Multiple sclerosis (MS) is one of the most studied neurological diseases, although scarce attention has been placed on symptomatic therapy. The aim of the study was to evaluate the frequency of medication prescription for the major symptoms related to MS in order to better understand the needs of patients. The study was conducted during an epidemiological survey in the province of Genoa, Italy. Out of 856 patients with MS in the study area, 665 agreed to participate in a structured interview. Two hundred and forty-nine (37%) subjects, with a mean age of 53 years and a mean Expanded Disability Status Scale (EDSS) score of 5.2, were taking at least one symptomatic medication. Four hundred and sixteen (63%) subjects, with a mean age of 49 years and a mean EDSS score of 4.5, were not using symptomatic therapy. The most commonly treated symptoms were pain (28%), spasticity (27%) and mood disorder (16%), while bladder dysfunction (8%) and fatigue (3%) were less frequently treated with medication. Seventy-seven patients (12%) were taking medications for reasons not directly related to MS. This cross-sectional study underlines the frequency of medication prescription for symptoms such as spasticity and pain, while other common symptoms, such as bladder dysfunction and fatigue, may perhaps be undertreated. The present findings also underline the need for clinical trials on symptomatic therapies.