With 37 places up for grabs in the group stage, past success will count for nothing as some of Europe's most illustrious names come up against lesser lights with plenty to prove.
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No fewer than 74 teams from 31 nations stretching from Madeira's CS Marítimo in the west to Russian side FC Sibir Novosibirsk in the east are in action on Thursday hoping to claim a place in the UEFA Europa League group stage.
So far only holders Club Atlético de Madrid are assured of a spot when the competition proper begins on 16 September, but otherwise past success will count for nothing as some of European football's most glamourous names rub shoulders with lesser lights looking to spring a surprise and write their own piece of history.
Six former European Champion Clubs' Cup winners are set to join the fray at this stage, taking the tally to eight given that Liverpool FC and Juventus both advanced from the third qualifying round. Of that number, 1988 winners PSV Eindhoven have already lost 1-0 to Sibir in the day's early kick-off while Qarabağ FK continue to fly the flag for Azerbaijan, this time up against the might of BV Borussia Dortmund.
While Qarabağ are bent on becoming the first Azerbaijani outfit to reach the group stage of a European club competition, Kazakhstan's FK Aktobe take on AZ Alkmaar with similar ambitions, as do Welsh champions The New Saints FC against PFC CSKA Sofia. TNS and Aktobe are two of 15 sides entering the competition after losing in the UEFA Champions League third qualifying round.
The spotlight will be on big-spending Manchester City FC as they travel to Romania to take on FC Timişoara in the first leg, and goalkeeper Shay Given admits his side have plenty to prove. "We have a strong squad so I'd imagine we're probably one of the favourites, but we've got to go out on the pitch and prove that," he told UEFA.com.
"It might be difficult for the manager to keep everyone happy, but we have got some very exciting players and some of the best players in the world as well, so it bodes for a very exciting campaign. The Europa League [means] there's a lot of games and the squad will be needed for those games, but we've got a strong chance of doing very, very well."
City are not the only side with big ambitions. After leading Fulham FC to the final last season, Roy Hodgson will be hoping to do even better at the helm of Liverpool, who meet Trabzonspor AŞ, while Luigi Delneri has set Juventus "no limit" in the competition ahead of their meeting with SK Sturm Graz.
There is even a rerun of last season's play-off between SK Rapid Wien and Aston Villa FC to whet the appetite. Villa may have lost manager Martin O'Neill, but defender Richard Dunne insists his side are still capable of avenging last year's defeat, telling UEFA.com it is time to "put that record right".