Cellular senescence is a process that results in irreversible cell-cycle arrest, and is thought to be an autonomous tumor-suppressor mechanism. During senescence, cells develop distinctive metabolic and signaling features, together referred to as the senescence-associated secretory phenotype (SASP). The SASP is implicated in several aging-related pathologies, including various malignancies. Accumulating evidence argues that cellular senescence acts as a double-edged sword in human cancer, and new agents and innovative strategies to tackle senescent cells are in development pipelines to counter the adverse effects of cellular senescence in the clinic. We focus on recent discoveries in senescence research and SASP biology, and highlight the potential of SASP suppression and senescent cell clearance in advancing precision medicine.