The expression of bcr-abl in chronic myelogenous leukemia leads to a large increase in the generation of mature myeloid cells. The key biochemical alteration in this disease is an increased Abl kinase activity. This up-regulation in activity is mediated through the binding of a portion of the Bcr molecule to the SH2 regulatory domain of the Abl protein. One effect of this alteration is a marked increase in resistance to drug induced cell death by apoptosis. This resistance can be overcome with the use of appropriate antisense oligonucleotides to the bcr-abl gene. The role and contribution of apoptosis to the development of the disease and the prospect of using antisense oligonucleotides as therapeutic agents is discussed.