This short review on current treatment options in chronic myeloid leukemia (CML) in the chronic phase summarizes the latest version of the ELN treatment recommendations dating from 2013 and indicates treatment situations not yet reflected in these recommendations. Daily practice in CML management is complicated by the recently observed treatment-emergent vascular and pulmonary adverse events in second- or later-generation tyrosine kinase inhibitors (TKIs), the lack of guidance with respect to the best TKI for initial treatment, as well as the optimal TKI sequence because no prospective randomized comparative data for second- and third-generation TKIs are available. Physicians have to balance the efficacy issues and safety aspects of the respective TKI and consider patient-specific factors such as comorbidities. Patients with any cardiovascular or pulmonary disease or treatment-requiring cardiovascular risk factor should receive nilotinib or ponatinib only if risk factors and comorbidities are treated accordingly and are further monitored. If these comorbidities are insufficiently controlled, other TKIs might be preferred. Dasatinib treatment should be critically evaluated in patients with pulmonary disease and other TKIs might be preferred in this setting. For as long as CML treatment is considered to be maintained lifelong, and no survival benefit for later-generation TKIs has been demonstrated, safety issues dominate the choice of treatment options. The concept of discontinuing TKI treatment after achieving a deep molecular response might in future change these considerations.