Chemotherapy-induced senescence leads to cancer cell survival and relapse. Chemotherapeutic drugs and p53-activating compounds cause tumor regression by inducing apoptosis in most cancer cells. A subset of cancer cells, however, is resistant to the treatment and undergoes senescence. This quiescence state endows cancer cells with a macrophage-like program that allows them to engulf neighboring cells and to persist over time until they ultimately drive relapse.