Senescence was rendered a tumor suppressor mechanism based on the observation of its protective effect against cancer in young organisms under conditions of oncogene activation or inactivation of tumor suppressor genes. In addition to this beneficial effect, senescence has been deemed to have age-associated deleterious effects because, apparently, senescence not only recapitulates aging and therefore loss of function and tissue regeneration capacity, but can also induce preneoplastic changes in adjacent stromal cells, provoke degenerative diseases or induce the production of tumor cell growth promoting factors. For that reason, senescence has become an attractive therapeutic target against cancer. This paper reviews some of the latest findings on the role of senescence in the malignant progression and analyzes them in relation to the concept of antagonistic pleiotropism, as well as its possible use as a therapeutic target against cancer.