Cancer patients report numerous adverse symptoms associated with their disease and treatment including cognitive dysfunction, fatigue, and affective distress. Cognitive dysfunction is ubiquitous in patients with primary central nervous system (CNS) cancer and recent evidence has documented similar deficits in patients with non-CNS cancer as well. Both the cancer itself and treatments including chemotherapy, biological response modifiers, and hormonal therapies have been demonstrated to adversely impact cognitive and neurobehavioral function. Neuroimaging and neurophysiological investigations have likewise revealed alterations in brain function that are helping to account for the nature of these cognitive disorders. Similarly, preclinical animal research is assisting to identify the pathophysiological mechanisms that underlie treatment-related neurotoxicities. The coalescence of multidisciplinary clinical and research efforts hold promise for the development of interventions that may offer neuroprotection in addition to currently available symptomatic therapies and cognitive rehabilitation techniques.