European champions Porto nine-time champion Real Madrid English champions Arsenal Spanish champions Valencia and German champions Werder Bremen all go into their last group matches still uncertain of further involvement in the competition.
Nine clubs have already made it through: Juventus and Bayern Munich from Group C Manchester United and Olympique Lyon (Group D) PSV Eindhoven (Group E) AC Milan and Barcelona (Group F) Inter Milan (Group G) and Chelsea (Group H).
So while those clubs can afford to be relatively relaxed about their final group games the tension elsewhere on players coaches and fans will be almost unbearable.
The Dragao Stadium will witness a night to remember on Tuesday as Porto crowned European champions in May battle to finish second behind Chelsea in Group H with a win against the man who led them to glory at Gelsenkirchen.
Jose Mourinho who masterminded winning five major trophies in two seasons at Porto including the UEFA Cup in 2003 and the European Cup last season returns to the city after moving to big-spending Chelsea in the close season.
Whatever feelings he may have for his former club will be forgotten as he continues his own personal quest to become the first coach ever to win the European Cup in successive seasons with different clubs.
He has requested extra security protection for his visit while on current form Porto might think about taking to the field with extra players to have any chance of winning.
Chelsea crushed Newcastle United 4-0 to stay five points clear at the top of the English Premier League on Saturday while Porto slumped to a 1-0 defeat at home to Beira Mar on Friday.
Portuguese league leaders Porto who have five points from their five group matches have to beat Chelsea to stand any chance of advancing with Paris St Germain (5 points) playing CSKA Moscow (4 points).
If PSG win they will go through because even if they finish on the same number of points as Porto they have a better head-to-head record. If PSG and Porto lose CSKA will advance.
The fate of Porto's illustrious Iberian rivals Real Madrid is also hanging in the balance in Group B which Dynamo Kiev lead on 10 points followed by Bayer Leverkusen and Real Madrid who both have 8 points.
Real travel to AS Roma already eliminated after taking just one point from their five matches while Leverkusen face Dynamo Kiev at home in the other game in the group on Wednesday.
If Real win they are through while if they draw and Leverkusen also draw Leverkusen will go through as they have a better head-to-head record against Real.
Kiev are still not certain of qualifying since if they lose to Leverkusen and Real beat Roma the Ukrainians will be out.
Arsenal who like Madrid also have their eyes on the main prize at least have their fate in their own hands.
Although they have won only one and drawn four of their five matches Arsenal (7 points) will advance with PSV Eindhoven (10 points) from Group E if they beat already-eliminated and winless Rosenborg Trondheim (2 points) at Highbury.
Despite a recent drop in their own high standards Arsenal should prove far too strong for the Norwegian champions even without the suspended Patrick Vieira and Lauren who were sent off against PSV two weeks ago.
However the north London side cannot afford to relax. Panathinaikos (6 points) will leapfrog Arsenal if they beat PSV at home and the English champions draw or lose.
Arsenal's domestic rivals Liverpool four-time European champions in the 1970s and 80s also face a nerve-wracking evening at Anfield where they take on Olympiakos Piraeus.
The Greek side lead Group A with 10 points followed by Monaco (9) and Liverpool (7). Monaco travel to Spain to face bottom-placed and eliminated Deportivo Coruna.
If Liverpool Monaco and Olympiakos all finish with 10 points Olympiakos and Liverpool will advance because they have better head-to-head records against Monaco. Liverpool will also go through if they beat Olympiakos 1-0 or by a two-goal margin.
The other key issue to be settled is the fate of Valencia and Werder Bremen in Group G one of whom will join Inter Milan in the knockout phase.
Inter (11 points) cannot finish lower than second but are unlikely to have to worry about that anyway as they face Anderlecht (0 points) at home having won 3-1 in Belgium in September.
Anderlecht are also likely to have to field third-choice keeper Jan Van Steenberghe after reserve keeper Daniel Zitka broke his arm in training on Sunday to joint first choice Tristan Peersman (Achilles) on the injury list.
Werder (10 points) travel to Valencia (7 points) needing just a point to qualify -- while Valencia can go through by virtue of a 1-0 win or a two-goal advantage after losing 2-1 in Germany in September.
While qualification for the knockout phase is paramount those who lose out this week and finish third in their groups will have the consolation of a UEFA Cup spot next year.