Infants born prematurely before 37 weeks of gestational age (GA) have particular anatomical, immunological and metabolic characteristics that predispose them, even in the absence of diseases at birth, to severe morbidity. Respiratory syncytial virus (RSV) is the leading cause of hospitalization for lower respiratory tract infections (LRTI) in the first year of life, as well as an important cause of respiratory outcomes as recurrent wheezing in industrialized countries or mortality in developing countries. Prematurity is an important risk factor for hospitalization for severe RSV disease, but epidemiological, environmental and demographic risk factors also play a role in RSV infection. Currently, there is no effective antiviral therapy for the treatment of RSV infection, nor the possibility of using maternal immunization or vaccination of children to prevent infection, although numerous preclinical and clinical studies are still ongoing. Passive immunization with palivizumab has been shown to be safe and effective in preventing RSV hospitalization in children at greater risk of contracting a serious infection. Costs associated with palivizumab prophylaxis and its monthly intramuscularly administration has prompted many health institutions of different countries to implement specific recommendations, with the aim of protecting at risk infants for whom RSV infection is likely to cause serious illness or death. The cost-effectiveness ratio of prophylaxis, related to reduce hospitalization costs and the impact of the burden of RSV disease worldwide, greatly affects the drafting and the adoption of specific recommendations and the adherence to them, concerning the passive immunization with palivizumab.