Malignant tumors and their various treatments such as chemotherapy, radiotherapy and hormonal therapy can deleteriously affect a large number of cancer patients and survivors on multiple dimensions of psychosocial and neurocognitive functioning. Oncology researchers and clinicians are increasingly cognizant of the negative effects of cancer and its treatments on the brain and its mental processes and cognitive outcomes. Nevertheless, effective interventions to treat cancer and treatment-related neurocognitive dysfunction (CRND), also known as chemobrain, are still lacking. The paucity of data on effective treatments for CRND is due, at least partly, to difficulties understanding its etiology, and a lack of reliable methods for assessing its presence and severity. This paper provides an overview of the incidence, etiology, and magnitude of CRND, and discusses the plausible contributions of psychological, motor function, and linguistic and behavioral complications to CRND. Strategies for reliable neuropsychological screening and assessment, and development and testing of effective ways to mitigate CRND are also discussed.