The increasing incidence of multidrug-resistant (MDR) Gram-negative infections necessitates the use of neglected antibiotics such as colistin, even in the paediatric field. The objective of this review was to evaluate the available clinical evidence regarding the effectiveness and safety of systemic colistin in children without cystic fibrosis (CF). Relevant articles were identified from PubMed, Cochrane and Scopus databases. Ten case series and fifteen case reports, including a total of 370 children, were eligible for inclusion in this systematic review. Only 17 of the children were included in studies published after 1977. A total of 326 children received colistin for the treatment of infections and 44 for surgical prophylaxis or prophylaxis of infections in burns patients. Regarding the clinical outcome, 271 of 311 children included in the identified cases series were evaluable. From these 271 children, 235 (86.7%) were cured of the infection, 10/271 (3.7%) improved, 6/271 (2.2%) deteriorated and 20/271 (7.4%) died. Fourteen (70%) of the 20 deaths were attributed to the infection. No infection occurred in the 44 reported children with burns or surgical morbidity who received colistin for prophylaxis. Of these 44 children, 9 (20.5%) died; all deaths were attributed to co-morbidity. Nephrotoxicity occurred in 10/355 (2.8%) of the evaluable children in cases series included in this review. Most of the identified relevant case reports focused on treatment complications. The available evidence, mainly from old case series, suggests that systemic colistin is an effective and acceptably safe option for the treatment of children without CF who have MDR Gram-negative infections.