Imatinib is an inhibitor of the ABL, platelet-derived growth factor receptors, and KIT tyrosine kinases. Given the pathogenetic role of the BCR-ABL tyrosine kinase in chronic myeloid leukemia, this was the first disease selected for clinical trials with imatinib. In the clinical trials, patients in all phases of the disease responded to imatinib and experienced minimal toxicity. Responses in patients with chronic phase disease have been durable, thus far. Clinical trials with imatinib were expanded and there are now examples of malignancies driven by each of the targets of imatinib where remarkable results have been seen. The rationale for the use of imatinib in these various diseases and the clinical trial results will be reviewed.