An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of multiple sclerosis, including spasticity and pain. Endogenous molecules with cannabinoid-like activity, such as the "endocannabinoids", have been shown to mimic the anti-inflammatory properties of cannabinoids through the cannabinoid receptors. Several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis. Indeed, they can down regulate the production of pathogenic T helper 1-associated cytokines enhancing the production of T helper 2-associated protective cytokines. A shift towards T helper 2 has been associated with therapeutic benefit in multiple sclerosis. In addition, cannabinoids exert a neuromodulatory effect on neurotransmitters and hormones involved in the neurodegenerative phase of the disease. In vivo studies using mice with experimental allergic encephalomyelitis, an animal model of multiple sclerosis, suggest that the increase of the circulating levels of endocannabinoids might have a therapeutic effect, and that agonists of endocannabinoids with low psychoactive effects could open new strategies for the treatment of multiple sclerosis.