Imatinib was the first signal transduction inhibitor used in a clinical practice. Imatinib prevents the BCR-ABL protein from playing its role in the oncogenic pathway in chronic myeloid leukemia (CML). Imatinib directly inhibits tyrosine kinase activity. Imatinib binds to BCR-ABL kinase domain. As a result, the transmission of proliferative signals to the nucleus is blocked and leukemic cell apoptosis is induced. The FDA has approved imatinib as first-line treatment for newly diagnosed CML in December 2002 following an International Randomized Study (IRIS), who started in June 2000(1).Results from this study show the effectiveness of imatinib and its superiority with respect to the rates of complete hematological response (CHR), major and complete cytogenetic response (MCyR, CCyR). Patients randomized to imatinib arm at 8 – year data cut off continue to have a durable hematologic and cytogenetic responses, low progression to AP or BC, and remarkable survival outcomes. An overall survival (OS) rate is 85% for patients receiving imatinib (93% when only CML-related deaths and those prior to stem cell transplantation are considered).The very first patient treated with Imatinib for the first time was in 2002 in a 69 years old patient which is still alive and well today.