Post-stroke cognitive impairment, depression, and fatigue are common, persistent, and disabling. This review summarizes current knowledge on the pathophysiology, assessment, and management of these debilitating neuropsychiatric sequelae of stroke. We briefly review evolving knowledge on the neural mechanisms and risk factors for each condition. We describe patient-reported outcome measures and clinician rating techniques that can be used to assist in screening and comprehensive assessment. We then discuss behavioral and pharmacologic management strategies. Heterogeneity of stroke remains a challenge in management and new research is still needed to optimize and personalize treatments for stroke survivors.