Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status. Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function. Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome. Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics. Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms. Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.