As the vast majority of infants tolerate infection with the respiratory syncytial virus [RSV] well and can be managed in the home, most should not be considered for RSV prophylaxis with palivizumab. However, there exists a subset of vulnerable infants in whom the consequences of RSV infection are greater, with an increased likelihood of intensive care admission and mechanical ventilation. These include children born extremely preterm with chronic neonatal lung disease and infants with haemodynamically significant cardiac disease in whom there exists level II evidence to suggest that palivizumab may reduce their risk of acquiring RSV by approximately 50%. The use of palivizumab varies considerably across the world, based largely on economic considerations. This article reviews the strategies developed to fight RSV infection, the evidence for the use of palivizumab and suggests a reasonable approach clinically and economically to the use of palivizumab, proposing its use selectively in the most vulnerable infants during the first six months of life.