Treatment of malignancies with chemotherapeutic drugs and/or radiotherapy is designed to eliminate the disease by depriving the tumor cell of its reproductive potential. Frequently, the desired effect of cell killing is achieved through the promotion of apoptosis; however, accumulating evidence suggests that apoptosis may not be the exclusive or even primary mechanism whereby tumor cells lose their self-renewal capacity after radiation or drug treatment, particularly in the case of solid tumors. While failure to undergo apoptosis in response to chemotherapeutic drugs or radiation may represent a mechanism of drug and radiation resistance, particularly in the case of leukemias and lymphomas, it is gradually being recognized that in the case of solid tumors, loss of reproductive capacity can occur through alternative pathways including reproductive cell death or mitotic catastrophe, through autophagic cell death, and as described below, through a terminally arrested state similar to replicative senescence. Studies building upon the phenomenon of replicative senescence in normal cells approaching the limit of their reproductive potential have identified a comparable senescence-like arrest as a component of the tumor cell response to chemotherapeutic drugs and radiation. This response, which has been termed "premature senescence", "senescence-like growth arrest", "stress-induced premature senescence", and "accelerated senescence", can also result from supraphysiological mitogenic signaling, sub-optimal culture conditions, and ectopic expression of oncogenes. Here, we will use the term "accelerated senescence" in our consideration of the morphological, biochemical, and molecular aspects of treatment-induced senescence, its relationship to classical replicative senescence, its prevalence in clinical specimens and the implications of accelerated senescence for the outcome of cancer therapy.