Osteopathic medicine is a form of complementary and alternative medicine. Osteopathic practitioners treat patients of all ages: according to the Osteopathic International Alliance's 2012 survey, about one-third of all treated patients are aged between 31 and 50 years and nearly a quarter (23.4%) are pediatric patients, with 8.7% of them being younger than 2 years. In 2013 a systematic review evaluated the effectiveness of osteopathic manipulative treatment (OMT) in pediatric patients with different underlying disorders, but due to the paucity and low methodological quality of the primary studies the results were inconclusive. The aim of this review is therefore to update the evidence concerning OMT in perinatal and pediatric disorders and to assess its clinical impact. Most published studies favor OMT, but the generally small sample sizes in these studies cannot support ultimate conclusions about the efficacy of osteopathic therapy in pediatric age. In turn, clinical trials of OMT in premature infants might represent an important step in the osteopathic research because they can address both cost-effectiveness issues, and an innovative, multidisciplinary approach to the management of specific pediatric diseases cared for by the same, common health care system. The available studies in neonatal settings provide evidence that OMT is effective in reducing the hospital length of stay of the treated infants, therefore, suggesting that robust cost-effectiveness analyses should be included in the future clinical trials' design to establish new possible OMT-shared strategies within the health care services provided to newborns.