First-line treatment for chronic myelogenous leukemia (CML) is imatinib, but some patients do not respond or develop resistance to the drug, leading to suboptimal responses. Dasatinib and nilotinib are approved second-line compounds for patients experiencing imatinib failure. In a prospective comparison of dasatinib with high-dose imatinib in patients who did not respond to first-line imatinib, dasatinib was more effective and well tolerated. Nilotinib also is effective, but cross-intolerance does occur in a substantial number of patients. This article explores the importance of suboptimal response to imatinib and the appropriate second-line therapy as well as nursing implications for caring for patients with CML.