Second-generation tyrosine kinase inhibitors (TKI 2) represent a recent important improvement in the treatment of Philadelphia positive leukemias. These agents are a suitable major option if resistance or significant imatinib intolerance occurs in chronic and accelerated phase CML. They are now introduced as first line therapy in chronic phase CML where they induce cytogenetic and molecular response rates never seen to date, which is promising for long-term survival. We propose here an analysis of the main current data available for the use of TKI 2 in CML.