Imatinib, a potent inhibitor of the oncogenic tyrosine kinase BCR–ABL, has shown remarkable clinical activity in patients with chronic myelogenous leukaemia (CML). However, this drug does not completely eradicate BCR–ABL-expressing cells from the body, and resistance to imatinib emerges. Although BCR–ABL remains an attractive therapeutic target, it is important to identify other components involved in CML pathogenesis to overcome this resistance. What have clinical trials of imatinib and studies using mouse models for BCR–ABL leukaemogenesis taught us about the functions of BCR–ABL beyond its kinase activity, and how these functions contribute to CML pathogenesis?