We're four games into the Premier League season - add into that the first international break, two rounds of Carabao Cup fixtures and the opening Champions League games - all meaning squads are starting to be tested.
Several managers have seen key players go down in the opening weeks, some of them new summer signings. In Manchester both Rayan Cherki and Matheus Cunha have already missed games for City and United respectively, whilst other clubs know some of their biggest names are out long-term.
The likes of Tottenham's James Maddison and Chelsea defender Levi Colwill are due to miss the entire campaign. Other players like Kai Havertz and Bukayo Saka are hoping to get back sooner rather than later, but still have a way to go.
We've seen over the years how the absence of key personnel can really hamper a team's ambitions at both ends of the table. Arsenal are among the title hopefuls having to use their squad depth to manage whilst Manchester City are also missing some key men.
We take a look across the top flight at those currently sidelined and when they may return as the games - domestically and in Europe - continue to come think and fast.
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ArsenalBukayo Saka (hamstring) Ben White (knee) and William Saliba (ankle) are all fitness doubts and will be assessed after Saturday's training session.
Mikel Merino and Viktor Gyokeres are both available after suffering head injuries.
Gabriel Jesus (knee) and Kai Havertz (knee) are both long-term absences.
Aston VillaBoubacar Kamara (hamstring) and Amadou Onana (hamstring) are both "close" to returning.
Youri Tielemans (calf) has no return date on his injury.
BournemouthEnes Unal (knee) is a "long-term" injury.
Bafode Diakite isn't 100 per cent fit, but should be available for the game.
Adam Smith (hamstring) is expected to be out for a “few more weeks”.
BurnleyJordan Beyer (Knee) and Zeki Amdouni (Knee) are both injured without return dates.
Jacob Bruun Larsen should make the squad after returning to training.
Lesley Ugochukwu is serving a one-match ban following his dismissal against Liverpool.
BrentfordGustavo Nunes (Hamstring) and Paris Maghoma (Hamstring) are both still two weeks away from returning.
Mikkel Damsgaard (Illness) missed the midweek Carabao Cup win but is in contention to play this weekend.

Adam Webster (Knee) and Solly March (Knee) are both out "long-term".
Jack Hinshelwood (Ankle) has no return date.
Maxim De Cuyper is also a doubt (Knee).
ChelseaLevi Colwill (Knee) will miss the majority of the season.
Benoit Badiashile (Knock) and Romeo Lavia (Muscle) have no set return date.
Liam Delap (Hamstring) will remained sidelined until December.
Crystal PalaceCheick Doucoure (Knee) is out for several months, while goalkeeper Walter Benitez (finger) is set to miss the next two weeks.
Eddie Nketiah (Hamstring) and Adam Wharton (Muscle) will return this weekend.
Caleb Kporha (Back) and Ismaila Sarr (Hamstring) have no return date.

Jarrad Branthwaite (Hamstring) and VItalli Mykolenko (groin) are both doubts for the Merseyside Derby with Liverpool. David Moyes also warned of 'other knocks'.
FulhamNone
LeedsDaniel James (Muscle) and Willy Gnonto (Calf) are both "doubts" for this weekend's game but Joel Piroe (Calf) is in contention for the game with Wolves.
Goalkeeper Lucas Perri is out with Karl Darlow starting in goal.
LiverpoolAlexander Isak is feeling the effects of his first competitive match in months, but should play some part against Everton.
Curtis Jones is ready to return after missing the last two matches.
Man CityMateo Kovacic (Achilles) is set to return in October whilst Rayan Cherki (Thigh) is due to be missing for two months.
Rayan Ait-Nouri (Knock) has no return date.

John Stones (Muscle) is in contention to return this weekend.
Omar Marmoush (Knee) is eyeing a return against Brentford on October 5.
Man UtdLisandro Martinez (Knee) has been missing long-term and has no return date, while Diogo Dalot (muscle) will miss out against Chelsea.
Matheus Cunha (Hamstring) and Mason Mount (Knock) are both back in the squad.
NewcastleJacob Ramsey (Ankle) will be out for a number of weeks whilst Yoane Wissa (unknown) has no return date. Fabian Schar (head) had to be replaced against Barcelona, with Eddie Howe waiting for updates.
Nottingham ForestAnge Postecoglou has said Murillo is a doubt for this weekend after suffering a knock that 'isn't too serious'.
Nicolas Dominguez (Knee) is set to return to training next week, but Ola Aina (Hamstring) is sidelined for an extended period
SunderlandDan Ballard (Groin) and Enzo Lo Fee are set to return against Aston Villa this weekend.
Aji Alese (Shoulder), Luke O'Nien (Shoulder), Dennis Cirkin (Wrist) and Leo Fuhr Hjelde (Achilles) have no return date but are taking "bit longer than expected".
Romaine Mundle (Hamstring) is set to return after the next international break.

James Maddison (Knee) will see him miss almost the entire season whilst Dejan Kulusevski (Knee) and Radu Dragusin (Knee) are also long-term absentees.
Dominic Solanke (Ankle) has returned to the grass, but will miss at least the next two matches.
West HamAaron Wan-Bissaka (Stomach) is unavailable for this weekend. Tomas Soucek is suspended after being red carded vs Tottenham.
WolvesLeon Chiwome (Knee) will miss the entire season whilst Jorgen Strand Larsen (Achilles) has returned to training and is set to play a part against Leeds.
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