With the resumption of the Champions League and Europa League on the horizon, some of Europe's biggest clubs will once again be forced to juggle their domestic duties with continental matters in the coming months.
It comes at a time where title challenges and relegation battles are shaping up throughout Europe and the rest of the world, and many managers will now be beginning to look at the run-ins their teams face.
This weekend the main focus is on England with derbies in London, Birmingham and Yorkshire, but there are also notable games in France, Spain and Germany, amongst others.
Here, Sports Mole rounds up the biggest, best and most important of the weekend's contests from all over the world.
Tottenham Hotspur vs. Arsenal (Saturday, 12.30pm)
Gameweek 27 of the Premier League season kicks off in style on Saturday lunchtime as Tottenham Hotspur welcome local rivals Arsenal to Wembley for the North London derby.
There are more than just bragging rights up for grabs this weekend, though, with both clubs currently sitting outside the top four in the Premier League table and defeat for either leaving them playing catch-up to an even greater extent.
It is Arsenal who arguably need the win most, with the Gunners currently five points off the Champions League places while Spurs are four points better off and would move into the top four - temporarily at least - as long as they avoid defeat.
Both will be going into the match in high spirits too; Spurs have successfully negotiated a difficult spell of fixtures so far, taking four points from matches against Manchester United and Liverpool before safely booking their place in the next round of the FA Cup on Wednesday night.
There is a fresh feel about Arsenal too, with their poor January form being somewhat forgotten due to some encouraging transfer business and a 5-1 victory over Everton last time out in which their new boys - amongst others - shone.
The Gunners also won the reverse fixture at the Emirates Stadium in November, although that is their only league triumph over their London rivals in the last seven attempts and they haven't won away to Spurs since 2014.
Aston Villa vs. Birmingham City (Sunday, 12pm)
As if the North London derby was not enough, the Second City derby - arguably English football's fiercest - also takes place this weekend as Aston Villa host Birmingham City at Villa Park.
The two teams go into the match with very different aims this season, though, as Villa look to return to the Premier League via automatic promotion while Birmingham are fighting simply to stay in the division.
Villa are just one point off second-placed Derby County as things stand and are the Championship's form side at the moment, having won each of their last six league games including all five so far in 2018.
Birmingham's own form should not be understated, though, as despite their relatively lowly league position of 19th, the Blues have won four of their last six league games and could win three on the bounce for the first time since October 2015 this weekend.
Indeed, Villa are one of only two teams to have picked up more points than their city rivals over the last six games, a run of form which has lifted Birmingham four points clear of the relegation zone.
However, the Blues have only won one of their last 13 meetings with Villa across all competitions and have not won a derby in the league since March 2005.
Saint-Etienne vs. Marseille (Friday, 7.45pm)
French football's two most successful clubs will do battle on Friday night when Saint-Etienne host Marseille at the Stade Geoffroy Guichard.
Paris Saint-Germain may have dominated the recent history of French football, but the capital outfit have still won four titles fewer than Saint-Etienne and three fewer than Marseille.
These two clubs have won 19 titles between them, although the most recent of Marseille's nine came in 2010 while 10-time champions Saint-Etienne haven't lifted the trophy since 1981.
Neither look like breaking their drought this season due to PSG's healthy lead, although Marseille do go into Friday's match sitting second in the table, 11 points adrift of the leaders but - more importantly - three above fourth-placed Lyon.
Marseille have also won eight and lost none of their last nine outings across all competitions and have scored a staggering 15 goals in their most recent two, thrashing Metz 6-3 last weekend before a 9-0 win in the cup on Tuesday night.
Saint-Etienne have won back-to-back games themselves to move four points clear of the relegation zone, but they were beaten 3-0 in the reverse fixture and have not won against Marseille in their last nine attempts.
Valencia vs. Levante (Sunday, 7.45pm)
La Liga plays host to the Valencian derby on Sunday evening when Valencia welcome local rivals Levante to the Mestalla.
It is a contest which could have a sizeable impact at both ends of the table, but particularly for the visitors with Levante currently sitting just one place above the relegation zone.
There is a three-point cushion separating them from the bottom three, though, and Levante are going into the match off the back of a memorable 2-2 draw with Real Madrid last weekend.
However, they have still failed to win any of their last 10 La Liga matches and have picked up maximum points on just three occasions all season, so their best hope may be adding to their league-high tally of 11 draws.
Valencia are in poor form themselves, though, losing each of their last three league matches and winning just three of their last 10, having won eight in a row prior to this dip in form.
Marcelino's side still sit in third place, but with only a three-point gap to fifth-placed Villarreal, a first win in three against their local rivals is of growing importance.
Sheffield United vs. Leeds United (Saturday, 12.30pm)
Paul Heckingbottom will get his Leeds United reign underway in a Yorkshire derby at Bramall Lane on Saturday knowing that he will need to hit the ground running if he is to rescue the club's playoff hopes.
Leeds disposed of Thomas Christiansen following a run of seven matches without a win across all competitions, including just two points from the last 18 on offer in the Championship to leave them bottom of the form table.
A seven-point gap has opened up between 10th-placed Leeds and the playoffs as a result, with Sheffield United one of the clubs currently between their opponents on Saturday and the top six.
The Blades are not in particularly good form themselves, though, winning just two of their last 13 Championship games to slip five points off the pace as well.
Saturday's hosts have won just one of their last seven home league games, and the smart money may be on a goalless draw this weekend with Sheffield United failing to score in their last three matches at Bramall Lane and Leeds drawing blanks in their last three away games.
Sheffield United did run out 2-1 winners at Elland Road in the reverse fixture, though, and have lost just one of their last 10 meetings across all competitions stretching back to 1993.
Other matches to look out for
Bayern Munich vs. Schalke: Runaway Bundesliga leaders Bayern Munich will look to extend their 11-match winning run against fifth-placed Schalke on Saturday, with the visitors one of four teams separated by one point in a fascinating race for Champions League football.
Barnsley vs. Sheffield Wednesday: Another Championship Yorkshire derby takes place on Saturday when Barnsley begin life after Heckingbottom against Sheffield Wednesday. Barnsley have won just one of their last 16 games across all competitions to leave themselves just one point and one place above the relegation zone, while Sheffield Wednesday are not yet safe themselves having only won one of their last 14.
Steaua Bucuresti vs. CFR Cluj: Romania's top two meet in a title battle on Saturday with only two points separating second-placed Steaua from the leaders Cluj, who are looking to win their first title since 2012.