Cow's milk allergy (CMA) is one of the most frequent food allergies in childhood with an estimated prevalence of 2% in infants. As observed in the natural course of this disease, CMA has a good prognosis and more than half of the children reach the tolerance before school age. Otherwise, many different factors can modulate the natural history of CMA. Clinical and laboratory data suggest that many endotypes and phenotypes can be individuated with different evolutions towards tolerance. For these reasons physicians need to identify these different patterns to better choose the therapeutic pathway for each patient. Another aspect is represented by the developing strategies of primary prevention of CMA, such as dietary interventions both in the mother (during pregnancy and/ or lactation), and, in absence of breast milk, also in high risk infants, through the use of extensive or partial hydrolyzed milk formula. Nevertheless many studies have been carried out, up today the available data are still conflicting and more robust results should be reported. The aim of this review article is to give practical advices in the diagnosis, management and prevention of CMA in childhood, according to the most recent guidelines and consensus documents.