Protein Tyrosine kinases (TKs) play important roles in regulating the most fundamental cell processes, such as the cell cycle, proliferation, differentiation, motility, and cell death or survival. In many tumor cells, key TKs may no longer be adequately controlled, and excessive phosphorylation sustains signal transduction pathways in an activated state. Imatinib mesylate is an oral multitargeted tyrosine kinase inhibitor with antitumor activity. It recently received approval from the US Food and Drug Administration for the treatment of patients with BCR/ABL translocation defining chronic myeloid leukaemia, and subsequently for the treatment of patients with KIT (CD117)-positive non-resectable and/or metastatic malignant gastrointestinal stromal tumors. It has also shown promising clinical activity against other advanced solid tumors. The review provides an updated summary of emerging clinical experience with this promising new anticancer agent.