Cancer and treatment-related neurocognitive dysfunction (CRND) – impairments in aspects of cognition commonly including attention and memory, information-processing speed, and executive functioning – can negatively affect patients' and survivors' participation in routine activities of daily living and overall quality of life. CRND can be enduring, and varies in severity level. The epidemiology of CRND is not yet clearly established; reported incidence has ranged from 17% to 75% among patients and survivors of noncentral nervous system malignancies, including breast, prostate, cervical, and colorectal cancers. Progress in the development of strategies for assessing and treating CRND has been delayed by limitations in the knowledge of the precise etiology of this adverse condition, as well as the lack of sufficiently sensitive and reliable methods to determine its presence and quantify its severity. In this chapter, we present a brief description of the concept of CRND and its clinical presentation, and discuss the descriptive epidemiology, pathophysiology, risk factors, and availability of treatment interventions. This neuroepidemiologic perspective provides a framework for characterizing CRND, determining its etiology, and understanding its negative effects on routine activities of daily living, to help support the development and testing of reliable interventions to treat this deleterious condition for patients and survivors.