The senescence-associated secretory phenotype (SASP) defines the ability of senescent cells to express and secrete a variety of extracellular modulators that includes cytokines, chemokines, proteases, growth factors and bioactive lipids. The role of the SASP depends on the context. The SASP reinforces the senescent cell cycle arrest, stimulates the immune-mediated clearance of potentially tumorigenic cells, limits fibrosis and promotes wound healing and tissue regeneration. On the other hand, the SASP can mediate chronic inflammation and stimulate the growth and survival of tumor cells. The regulation of the SASP occurs at multiple levels including chromatin remodelling, activation of specific transcription factors such as C/EBP and NF-κB, control of mRNA translation and intracellular trafficking. Several SASP modulators have already been identified setting the stage for future research on their clinical applications.