Here's a look at four possible candidates for the chancellery from Merkel's CDU/CSU conservative bloc.
Avenger: Friedrich Merz
Friedrich Merz, 64, has never forgiven Merkel for driving him out as head of the party's group of MPs in the Bundestag in 2002.
He was narrowly beaten in the vote for party leader by Merkel's preferred successor Kramp-Karrenbauer in December 2018, and has been waiting in the wings ever since.
He announced this month he was quitting his job on the supervisory board of the German arm of investment firm BlackRock to dedicate himself to politics and helping the CDU “renew itself”.
Favoured by the CDU's most conservative members, Merz wants to shift the party to the right to woo back voters lost to the anti-Islam, anti-immigrant AfD.
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Compromise: Armin Laschet
State premier of Germany's most populous region North Rhine-Westphalia, 58-year-old Armin Laschet could emerge as the compromise candidate.
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A political veteran who has served in the national parliament and the European Parliament and as families minister in Merkel's first government, Laschet has often backed her moderate course.
He has won plaudits for his tough stance against criminal gangs in his state, while his liberal leanings make him acceptable to Merkel's centre-left coalition partner, the Social Democratic Party (SPD).
'Anti-Merkel': Jens Spahn
At just 39 years old the youngest potential candidate, the ambitious Health Minister Jens Spahn is seen by many as the “anti-Merkel”.
Highly critical of Merkel's decision to open the door to an influx of asylum seekers in 2015, he is liked by the CDU's more right-wing faction.
“Spahn would represent a new start,” the conservative Frankfurter Allgemeine daily said, seeing in him “a brave party leader” and “potent” possible chancellor.
Long shot: Markus Söder
The 53-year-old leader of Merkel's Bavarian CSU sister party is seen as having a more distant shot at the chancellery -– and may not even want to throw his hat in the ring.
Long a defender of traditional Christian values as Bavaria's state premier, Söder has in recent months tried to soften his image, notably by calling for more climate protection.
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He unequivocally condemned last week's vote fiasco in the state of Thuringia, where regional CDU lawmakers broke a taboo by voting in the same camp as the far-right AfD to oust a state premier.
Söder called the vote “an unacceptable breach in the dam”, winning praise for his firm stance while Kramp-Karrenbauer and the CDU scrambled to contain the fallout.