Although spasticity of varying severity affects up to 80% of patients with multiple sclerosis (MS) during the course of their disease, the symptom is often overlooked and undertreated. Despite the availability of oral antispasticity treatments (baclofen, tizanidine and others), approximately one-third of MS patients in Europe and the USA experience moderate or severe nonfocalized spasticity. At present, a thorough clinical evaluation of MS-related spasticity that takes into account the patient's own perception of spasms, spasticity-related pain and other associated symptoms is not common in daily neurological practice. Some of the usual spasticity scales, such as the Ashworth and modified Ashworth scales, reflect the observer's measurement of spasticity at a particular point in time. Herbal (smoked) cannabis has long been recognized as a possible option for relief of spasticity and neuropathic pain, but pertinent concerns about psychoactive effects and addiction risk have prevented its common use. An innovative method of benefiting from the mode of action of cannabinoids while limiting their drawbacks is to reduce peak plasma levels of 9-delta-tetrahydrocannabinol and counteract psychoactivity with higher than naturally occurring proportions of a second cannabinoid, cannabidiol. Sativex® oromucosal spray (1:1 ratio of 9-delta-tetrahydrocannabinol/cannabidiol) has recently been approved in a number of EU countries and elsewhere for use in patients with MS-related spasticity who are resistant to treatment with other antispasticity medications. In clinical trials, Sativex provided initial relief of spasticity symptoms within the first 4 weeks of treatment (trial period) in up to about half of patients resistant to other available oral antispasticity medications and demonstrated clinically significant improvement in spasticity (30% or higher reduction from baseline) in three-quarters of the initial responders. Adverse events were limited mainly to mild or moderate cases of somnolence and dizziness. Under everyday clinical practice conditions, Sativex at a mean daily dose of <7 sprays/day, was shown to relieve spasticity in about 70% of patients previously resistant to treatment. Clear improvements were also noted in associated symptoms such as sleep disturbances, bladder problems, loss of mobility and cramps. In large observational studies, >80% of patients reported no adverse events with the use of Sativex and interim data from safety registries in the UK and Spain indicate a low risk for serious adverse drug reactions. Follow-up studies in Sativex responders support continued benefit without the need to increase doses for at least 1 year. Sativex appears to be a promising solution for a meaningful proportion of patients with MS-related spasticity who have inadequate response to current antispasticity medications.