Updated findings from a randomised comparison of imatinib versus previous standard treatment in the treatment of newly diagnosed chronic myeloid leukaemia suggest that this first-generation tyrosine-kinase inhibitor can induce excellent long-term responses in most patients. However, a small proportion of patients will not respond or will lose previous responses, and, for these patients, alternative treatments are needed. This review is the second of two parts: the first part provided a review of the mechanisms underlying resistance to imatinib and this second part will discuss the management of patients who are resistant to imatinib by reviewing the many new drugs being introduced into clinical practice and suggesting strategies for decision making.