Defects in the programmed cell death mechanisms can extend cell lifespan, contributing to neoplastic cell expansion independently of cell division. Deficiencies in apoptosis also contribute to carcinogenesis by creating a permissive environment for genetic instability and accumulation of gene mutations, permitting disobeyance of cell cycle checkpoints which would normally induce apoptosis, facilitating growth factor- and hormone-independent cell survival, supporting anchorage-independent survival during metastasis, reducing dependence on oxygen and nutrients, promoting resistance to immune-based destruction, and conferring resistance to cytotoxic anticancer drugs and radiation. Though much remains to be learned, identification of gene families that control the physiological cell death pathway has provided the basis for improved understanding of tumor biology. This review describes some of the recent progress made towards delineating the biochemistry and molecular biology of apoptosis control, and briefly summarizes the progress in identifying specific road blocks to apoptosis induction in cancers. These advances are beginning to reveal novel strategies for combating cancer by restoring apoptosis sensitivity.