Pediatric-onset multiple sclerosis (POMS) has distinctive features compared with adult-onset multiple sclerosis (AOMS), and warrants caution despite being a rare form of MS. POMS diagnostic criteria are somewhat different from those used in AOMS, with acute disseminated encephalomyelitis being a key differential diagnosis of MS in children. Other differential diagnoses that have to be ruled out before diagnosing MS include demyelinating syndromes, autoimmune and systemic pathologies, and infectious, genetic, metabolic and neoplastic diseases. Compared with AOMS, POMS has several different clinical, biological and imaging findings. At onset, high-level inflammatory activity is mainly reported, and patients with POMS are also at high risk of developing early physical disabilities and early cognitive impairment. Yet, treating patients with POMS is challenging due to a lack of randomized controlled trials. Some of the disease-modifying drugs currently prescribed are analogous to therapies used in adults, and are associated with good tolerability in pediatric patients. However, a few clinical trials dedicated to POMS are now in progress, and the future outlook is to improve the long-term prognosis of POMS patients with early effective and safe treatments.