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Chronic myeloid leukaemia (CML) is a clonal disorder of the haemopoietic stem cell arising as a consequence of the formation of the bcr-abl oncogene. The particular molecular basis of this condition has enabled the development of therapies that selectively target diseased cells. The success of the rationally designed first-line therapy imatinib mesylate (IM) is tempered by the problems of disease persistence and resistance. Novel strategies have been identified to take forward therapy in CML and these will be discussed in this review. This work is generated from a review of published literature and contains particular insight into the work performed by our group in this field.