Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is a neoplastic hematologic disorder, which is a functionally curable chronic disease via using tyrosine kinase inhibitor (TKI) drugs. The life expectancy for the vast majority of chronic phase-CML patients is "normal", thanks to the unique effectiveness of the ABL-targeted TKIs of CML. The patients with CML receiving TKI could be expected to have a survival and 'quality of life' of the age- and sex-matched healthy people. Several TKI pathways may be selected for the first line CML treatment, including first-generation original/generic imatinib or second-generation TKIs, such as bosutinib, nilotinib, and dasatinib. Individual characteristics of the CML patients, TKI drug compliance, lifestyle preferences, comorbidities, distinct toxicity profile of the TKI drug, and physician-clinical center experience are among the critical factors to be taken into account while deciding on the proper first line TKI in the newly diagnosed CML patients. Identifying CML patients at a higher risk for the disease progression or TKI resistance is essential and could influence the choice of primary TKI. The optimized integrations of the best available evidence, individual patient characteristics, and physician clinical experience are required in order to select best TKI for the CML management. Pathobiological basis depending upon the prospective in vivo research data is also crucial during the follow-up as well.