Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). Although these treatments have changed the natural course of CML and many other cancers, they may cause cardiovascular and/or metabolic complications. In this review, we discuss how overlooking the main drivers of cardiovascular events (CVEs) and lack of standard definitions for cardiovascular adverse events might have affected these event rates in CML trials. Methodological limitations that affect the available data are discussed, with an emphasis on the future direction of cardiovascular safety research in trials of investigational drugs in cancer treatment.