This chapter discusses the epidemiology, sites of strokes, clinical presentation, pathophysiology, and treatment options for central post-stroke pain (CPSP). CPSP occurs after lesions at any level of the somatosensory pathways of the brain extending from the medulla to the thalamus to the somatosensory cortex. The diagnosis of CPSP is based on a history of stroke followed by pain within an area of the body corresponding to the presumed lesion of the central nervous system with confirmation of the lesion by imaging. The pharmacological and non-pharmacological management of CPSP is challenging and is complicated by comorbid depression, anxiety, and sleep disturbances which are common in this patient population. Tricyclic antidepressants and the anticonvulsant lamotrigine are first-line analgesics in the management of CPSP. Although the prevalence of CPSP is relatively low, the pain can be resistant to treatment and can have a major impact on quality of life.