Die Werkself fell just six points short of a top-four finish last term and will need to pick up as many points as possible against less-fancied sides if they are to challenge for one of the coveted UEFA Champions League places this time around.
Champions League cravings
Sami Hyypia's charges kick-off their Bundesliga campaign with prized duo Andre Schürrle and Lars Bender still in tow. The German internationals were key factors in Leverkusen's superb finish to 2011/12, when they recorded four wins and two draws from their final six games to secure a European berth.
Moving forward, Hyypia's vast experience is is likely to be crucial in the quest for Champions League football - the former Leverkusen defender won the Champions League, UEFA Cup and FA Cup during his Liverpool days.
Out to avoid the drop
Facing potential top-four opposition on Matchday 1 presents baptism of fire for Eintracht Frankfurt, who made light work of life in Bundesliga 2, spending just one season in the second tier before returning to the top flight in second place. Armin Veh's side looked to be picking up momentum during pre-season too, but a first-round DFB Cup defeat at Erzgebirge Aue has dampened the mood somewhat.
The battle to avoid the drop is set to be fierce with three from as many as eight clubs plausible relegation fodder, so it's Eintracht's previous experience in the division that could nudge them to safety. They'll need goals either way, with much resting on Olivier Occean's transition from Bundesliga 2, where, along with Frankfurt forward Alex Meier, he netted 17 goals in 31 appearances for former club SpVgg Greuther Fürth.
Hole at the back
Eintracht won 20, drew eight, lost six and conceded just 33 goals on their way back to the Bundesliga last term, but Armin Veh is going to have to ensure his defence are fully focused if they are to avoid a similar hiding to that which Leverkusen handed Carl Zeiss Jena in the first round of the DFB Cup last weekend.
The good news for Veh's side is that Leverkusen hit the net a paltry 52 times last term - their lowest haul in nine years - and one final omen that might swing it in Frankfurt's favour as football celebrates the Bundesliga in its 50th year is that Eintracht, exactly 25 years ago to the day, earned a 3-1 win over none other than Bayer 04 Leverkusen.
Frankfurt: Trapp - S. Jung, Zambrano, Anderson, Oczipka - Rode, Schwegler - Aigner, Meier, Inui - Occean
Leverkusen: Leno - Schwaab, M. Friedrich, Wollscheid, Kadlec - L. Bender, Reinartz, Rolfes - Schürrle, Bellarabi - Kießling