Recently, there has been renewed interest in the study of cognitive fatigue. It is known that fatigue is one of the most disabling symptoms in numerous neurological populations, including stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. Behavioral studies of cognitive fatigue are hampered by lack of correlation of self-report measures with objective performance. Neuroimaging studies provide new insight about cognitive fatigue and its neural correlates. Impairment within the cortico-striatal network, involved in effort–reward calculation, has been suggested to be critically related to fatigue. The current review surveys the recent neuroimaging literature, and suggests promising avenues for future research. Learning Objectives: As a result of reading the article the reader will be able to: (1) Describe types of fatigue and their manifestation in neurological disorders. (2) Understand further basal ganglia neuroanatomy and the role of the basal ganglia in cognitive fatigue.