Chemotherapy of malignant tumors including acute leukemias is largely based on empirical data and clinical experience. In the recent years it has become clear that anticancer drugs induce apoptosis in target cells. Drug-induced activation of apoptosis pathways appears to include parallel or sequential activation of death receptor systems and, most importantly, changes in mitochondrial function with concomitant release of apoptogenic factors leading to activation of downstream caspases. The identification of the critical elements of drug-induced apoptosis and activation of effector caspases will certainly provide new insights into the molecular determinants of chemosensitivity or chemoresistance of malignant tumors and leukemias.