Third-placed Schalke 04, three points ahead of Bayer Leverkusen, have the best chances to keep their place with a win over 17th-placed Nuremberg and grab the last automatic Champions League group stage spot.
Schalke, who competed in Europe's premier club competition this season as well, could successfully complete a roller-coaster season with a strong finish.
They could be boosted by the presence of captain Benedikt Hoewedes, back from injury as the defender races to be fit this week.
"I really want to help the team reach its goal," said Hoewedes after returning to team training this week following more than a month out with a muscle injury.
"I feel 100 percent and I have full confidence that I can play from the start. But at the end this is not about me but about the club."
"We only need a point but we will play to win with our attacking game."
Schalke will also have winger Jefferson Farfan back but will be without suspended top striker Klaas-Jan Huntelaar.
Their opponents are desperate for a win that could possibly see them snatch the relegation-playoff spot from Hamburg SV, who are a point ahead in 16th.
Combined with a Leverkusen win against visiting Werder Bremen that is also the only scenario for Schalke to miss out on the third spot.
With the fourth place leading to the Champions League qualifying rounds, Leverkusen will have to keep an eye on the rear view mirror with VfL Wolfsburg and Borussia Moenchengladbach in with a chance to finish fourth.
In-form Wolfsburg, in fifth place a point behind Leverkusen, take on Gladbach in a crunch match with Borussia two further points behind in sixth.
At the other end of the table Hamburg's stadium clock counting the total years, months, days and hours the team has been in the Bundesliga would have to be turned back to zero if they fail to equal or better the results of Nuremberg and last-placed Eintracht Braunschweig.
Former European champions Hamburg, a point ahead of Nuremberg and two above Braunschweig, are the only team to have played every season in the Bundesliga since the league's creation in 1963, rightfully earning the nickname 'dinosaur'.
When they travel to European hopefuls Mainz 05 on Saturday their thoughts will only be on holding on to the Bundesliga lifeline as they cannot catch up 15th-placed VfB Stuttgart any more to secure an automatic Bundesliga spot for next season.
- Sports & Recreation
- Bayer Leverkusen
- Schalke 04