Respiratory syncytial virus (RSV) is the leading cause of respiratory tract infection in infants and young children throughout the world. Although preterm birth has been considered for years the major risk factor for severe disease and hospitalization, recent findings indicate that prematurity is not a necessary condition, but one of the independent risk factors for severe RSV infection, together with chronic lung diseases, congenital heart disease and immunodeficiency. Furthermore, over 50% of infants hospitalized for RSV infections during the first year of life are healthy, full-term newborns, suggesting that other environmental and individual factors may be involved. Unfortunately, there is still no specific therapy against RSV infection and therefore prophylactic measures seem to be the only intervention to avoid disease complications. No safe and effective RSV vaccine is available for the prevention of serious RSV infection. Therefore, in addition to hygienic measures, the only approach is passive immunoprophylaxis with humanized monoclonal anti-RSV antibodies, such as palivizumab that have been developed for clinical use. Because of the high cost of these antibodies, a better definition of the individual risk profile for severe RSV infection and timing of administration is needed for optimal effectiveness and careful use of limited health care resources. In this article, we have reviewed the clinical and pharmacological aspects of immunoprophylaxis with monoclonal antibodies for preventing RSV infection in high-risk infants.