Apoptosis, called programmed cell death, is one of the most important cellular mechanisms regulating the elimination of harmful and unnecessary cells. This tightly regulated suicide program is very important in the development and maintenance of tissue homeostasis. Disruption of apoptosis, also called natural defense mechanism, causes abnormal cellular proliferation and the emergence of genetic defects. Disruption of the apoptotic mechanism often results in tumorigenesis. Apoptosis can be induced by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as binding of ligands to death receptors on the cell surface. Apoptotic signaling pathways are regulated by many proteins, including BCL-2 family proteins, apoptosis inhibitor (IAP) proteins, and FLICE-inhibitor protein. This book chapter includes a review of the signaling pathways associated with apoptosis.