BCR–ABL-targeting tyrosine kinase inhibitors (TKIs) constitute the cornerstone of treatment for chronic myeloid leukemia. Although these agents are normally safe and effective, they can cause side effects that lead to intolerance and necessitate switching to an alternative treatment. In this review, we describe side effects that occur during treatment with imatinib, nilotinib or dasatinib—the currently approved TKI treatments for chronic myeloid leukemia—including class effects and key differences in safety profiles. We also describe how common side effects can be effectively managed and offer a working definition of intolerance that may be useful to clinicians when they consider switching between TKIs.