Central neuropathic pain is caused by a disease or lesion of the brain or spinal cord. It is difficult to predict which patients will develop central pain syndromes after a central nervous system injury, but depending on the etiology, lifetime prevalence may be greater than 50%. The resulting pain is often highly distressing and difficult to treat, with no specific treatment guidelines currently available. This narrative review discusses mechanisms contributing to central neuropathic pain, and focuses on pharmacological approaches for managing common central neuropathic pain conditions such as central post-stroke pain, spinal cord injury-related pain, and multiple sclerosis-related neuropathic pain. Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids have some evidence for efficacy in central neuropathic pain. Medications from other pharmacologic classes may also provide pain relief, but current evidence is limited. Certain non-pharmacologic approaches, neuromodulation in particular, may be helpful in refractory cases. Emerging data suggest that modulating the primary afferent input may open new horizons for the treatment of central neuropathic pain. For most patients, effective treatment will likely require a multimodal therapy approach.