Bcr-Abl tyrosine kinase inhibitor (TKI) is the initial choice of treatment for most patients with Chronic myelogenous leukemia (CML). In more than 90% cases CML is caused by chromosomal abnormality resulting in the formation of a so-called Philadelphia chromosome. This abnormality was discovered by Janet Rowley in 1972 and is due to fusion between Abelson (Abl) tyrosine kinase gene at chromosome 9 and break point cluster (Bcr) gene at chromosome 22. This results in a constitutively active Bcr-Abl tyrosine kinase and has been implicated in the pathogenesis of CML. Compounds have been developed that selectively inhibit the Bcr-Abl tyrosine kinase that results from a chimeric Bcr-Abl oncogene. Before the FDA approval of imatinib in 2001 no drugs were used that changed the natural progression of CML, only cytotoxic drugs such as busulfan, hydroxyurea or interferon-alpha (rIFN-α). Even though the first Bcr-Abl tyrosine kinase was named “the magic bullet” to cure cancer by The Times a second generation of Bcr-Abl TKI has been developed as a cause of resistance to imatinib. The resistance in patients is mainly caused by point mutations within the Abl kinase domain, over-expression of Bcr-Abl, increased production of transmembrane plasma proteins or constitutive activating of downstream signaling molecules such as Src-family kinases. Most of the drugs are adenosine triphosphate (ATP)-competitive inhibitors.[1]