Chronic myeloid leukemia (CML) is rare in children but presents a unique challenge as recent drug innovations have turned CML into a chronic disease with implications for treatment into adulthood. With the approval of newer-generation tyrosine kinase inhibitors (TKIs) in addition to imatinib, providers have more options for the treatment of chronic-phase CML (CML-CP) in children. The second-generation TKIs approved for use in children, nilotinib and dasatinib, have higher response rates than first-generation imatinib; however, overall survival rates appear to be the same. Even more options may soon become available with ongoing investigations into the use of bosutinib and ponatinib and other new agents in children. Possible long-term side effects of TKIs, including growth failure, should be carefully acknowledged by the treating provider. Although these known associations may not preclude treatment, providers should be aware of them to guide their management of pediatric patients with CML being treated long term with TKI therapy. Treatment-free remission is a desired goal for pediatric patients and providers alike, but current recommendations are for attempts at achieving this to be restricted to clinical study settings.