Pediatric cerebrospinal multiple sclerosis (MS) constitutes about 2-5% of all MS cases. The International Pediatric MS Study Group (IPMSSG) applies diagnostic criteria for adults to MS in childhood and adolescence. Recent publications highlight an increasing number of MS in children resistant to the first-line treatment, i.e. disease modifying therapy (DMT). Furthermore, the number of published case studies on children with highly active MS treated with natalizumab also rises, whereas long-term risks as well as therapeutic potential of this therapy in pediatric population have been at the centre of attention. This paper presents a group of 5 children in whom natalizumab was selected to manage highly active disease or resistance to conventional MS treatment and provided very good clinical as well as MRI results.