Chronic myeloid leukaemia (CML) is a paradigmatic disease, as knowledge on the molecular pathology of CML has driven the development of targeted drugs, which finally led to a substantial improvement of the patients' prognosis. However, despite very potent drugs, such as Imatinib, Nilotinib and Dasatinib for first- and second-line therapy are available, there is still place for improvement. Especially, selection of highly resistant T315I mutated clones represents a relevant clinical problem. The highlight of the 52nd Annual Meeting of the American Society (ASH) in 2010 for CML patients was data marking a profound step forward for patients developing a T315I mutation by providing safety and first efficacy results from a clinical trial testing Ponatinib, a TKI targeting T315I-mutated CML. These very early results from a small patient cohort provide a rationale basis for prospective testing of the drug in T315I-mutated CML and will help to further complement the "TKI cocktail" now available for CML patients.