Pain is a major matter for patients with multiple sclerosis; treatment response is frequently inadequate, with a significant impact on quality of life. The estimated prevalence of pain in multiple sclerosis ranges widely (26-86%), and different subtypes of pain, mediated by specific pathophysiological mechanisms, are described. The aim of this narrative review, performed using a systematic search methodology, was to provide current, evidence-based, knowledge about the pharmacological treatment of the different kinds of pain in multiple sclerosis. We searched for relevant papers within PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Clinical Trials database (ClinicalTrials.gov), considering publications up to November 2019. Two authors independently selected studies for inclusion, data extraction, and bias assessment. A total of 27 randomized controlled trials were identified, but in only a few cases, patients with different pain qualities were stratified. Following a mechanism-based approach, treatment of paroxysmal pain and painful tonic spasms should be based on sodium-channel blockers, whereas treatment of ongoing extremity pain should be based on gabapentinoids and antidepressants.