The tumor suppressor protein p53 controls cell cycle checkpoints and apoptosis via the transactivation of several genes. However, data from various laboratories suggest an additional role for p53: transcription-independent suppression of homologous recombination (HR). Genetic and physical interactions among p53, HR proteins (e.g. RAD51 and RAD54) and HR-DNA intermediates show that p53 acts directly on HR during the early and late steps of recombination. Complementary to the MSH2 mismatch-repair system, p53 appears to impair excess HR by controlling the minimal efficiency processing segment and by reversing recombination intermediates. By controlling the balance between the BLM and the RAD51 pathways, this direct role of p53 could maintain genome stability when replication forks are stalled at regions of DNA damage. In this article, we discuss the direct role of p53 on HR and the consequences for genome stability, tumor protection and speciation.