Why do former first ladies run for political office? Seventeen former first ladies ran for the presidency, vice presidency or Congress between 1990 and 2016, but the scholarly literature has failed to systematically analyze this phenomenon. We argue that former first ladies run for office when they have political ambitions and when the sociopolitical context offers them an opportunity to be competitive candidates. We analyze the 88 former first ladies who were available to run for office in 133 elections in 18 Latin American countries from 1990-2016. To test our argument, we conduct discrete-time duration models. The findings demonstrate that political ambition is the main factor that explains why former first ladies run for office. We also show that politically ambitious first ladies behave strategically, taking advantage of the opportunities they have to become candidates.