Apoptosis is the primary means by which most radio- and chemotherapy modalities kill cancer cells, and abnormalities in the apoptotic pathways may contribute to disease pathogenesis of cancer. Multiple Myeloma (MM) is a hematological malignancy which will affect 14,000 new individuals in the United States in 2001 and remains irreversibly fatal despite all available therapies. The current review focuses on the studies of apoptotic and survival signaling pathways in MM cells, which have both identified novel apoptotic and anti-apoptotic proteins and provided targets for novel therapeutics.