Drug-resistant paediatric tuberculosis (TB) is an overlooked global problem. In Italy, the epidemiology of TB has recently changed and data regarding drug-resistant forms in the paediatric setting is scanty. The aim of this case series was to report the cases of drug-resistant TB, diagnosed between June 2006 and July 2010 in four Italian tertiary centres for paediatric infectious diseases, in children and adolescents living in Italy. Twenty-two children were enrolled, of these 17 were resistant to one or more drugs and five had multidrug-resistant TB. All but one child were either foreign born or had at least one foreign parent. Twenty-one patients completed their treatment without clinical or radiological signs of activity at the end of treatment, and one patient was lost to follow up. The outcomes were good, with few adverse effects using second-line anti-TB drugs. Although this series is limited, it might already reflect the worrisome increase of drug-resistant TB, even in childhood.