The Authors report their experience related to 15 cases of neonatal osteo-arthritis which have occurred in the last seven years in the neonatal intensive care unit. Besides the traditional clinical picture, it is stressed that neonatal osteo-arthritis has recently acquired new interest for an etiologic shift of the pathogens and for the availability of new antimicrobial agents. The rational antibiotic treatment and the role of the coordinated medical and orthopedic therapy have been essential for the benign clinical course and for the long-term prognosis. It is concluded that in order to reduce this serious disease it is necessary to avoid every potential risk factor, to operate in rigorous aseptic conditions and to improve the environmental conditions of the neonatal intensive care units.