Treatment-free remission is now regarded as a primary aim of patients with long-term chronic myeloid leukemia (CML). Starting with the approval of imatinib in 2001, the effectiveness of tyrosine kinase inhibitors (TKIs) has resulted in significant improvements in outcomes for CML patients, and with that success has come a focus on discontinuing treatment in patients when appropriate. Results from trials such as the DADI (Dasatinib Discontinuation) and the STIM (Stop Imatinib) trials suggest this approach is feasible, and the National Comprehensive Cancer Network has modified its guidelines by incorporating TKI discontinuation in appropriately selected patients. There are a number of factors that go into the decision to stop TKI treatments. They do come with side effects, as well as an accompanying impact on a patient's quality of life. These can include fatigue, nausea, sleep disturbance, and depression. Other issues include concerns about drug-drug interactions, financial toxicity related to treatment, as well as cardiovascular safety issues associated with second- and third-generation TKIs.