Apoptosis, the cells intrinsic death program, plays an important role in the regulation of tissue homeostasis. Imbalances between cell death and survival may result in premature death, uncontrolled proliferation or tumor formation. Also, killing of cancer cells by various cytotoxic approaches such as anticancer drugs, γ-irradiation, suicide genes or immunotherapy, is predominantly mediated through induction of apoptosis in target cells. Thus, defects in apoptosis programs that suppress cell death can also confer drug resistance. Understanding the molecular events that regulate apoptosis and how tumor cells evade apoptotic deletion have provided a paradigm to link cancer genetics and response to cancer therapy. Insights into the signaling cascades that regulate drug-induced apoptosis provide rational targets for therapeutic interventions. Also, genetic variability in apoptosis regulatory genes found in tumors of individual patients may contribute to variability in drug response. Thus, monitoring expression profiles of apoptosis genes in tumors of individual patients or in response to specific pharmacological agents may serve as predictive markers of drug response.