The blast phase, sometimes referred to as “blast crisis,” of chronic myeloid leukemia (CML) remains a potentially life-threatening hematologic emergency and a clinical challenge. The advent of tyrosine kinase inhibitors has modestly improved survival in this setting, although outcomes remain unsatisfactory. CML in blast phase also imposes many challenges to the clinician and intensivist as it frequently manifests with potentially fatal complications such as hyperleukocytosis and leukostasis, tumor lysis syndrome, and disseminated intravascular coagulation. In this chapter, we present a contemporary overview of the epidemiology, pathophysiology, clinical manifestations, and management approach of blast phase in chronic myeloid leukemia, from an intensivist’s perspective.