Cellular senescence is a response to nonlethal intrinsic or extrinsic stress that results in persistent growth arrest with a distinct morphological and biochemical phenotype. The engagement of senescence may represent a key component for therapeutic intervention in the eradication of cancer. Nevertheless, for many years, the role of senescence in opposing tumour growth in vivo had previously been underestimated. The potential role of cellular senescence in anti-cancer therapy may be particularly attractive in advanced age, because of the age-related changes occurring at the level of both tumor suppressor genes and immune functions. This review, which is focused on the impact of cellular senescence in aging and cancer, summarises the intrinsic pathways and the molecular and epigenetic changes involved in the induction of cellular senescence, and analyzes the changes occurring at the level of these pathways during aging and cancer.