Respiratory syncytial virus (RSV) is the leading cause for childhood hospitalization and respiratory distress, being recognized as a major health and economic burden worldwide. RSV can exploit host immunity and cause a strong inflammatory response that leads to lung damage and virus dissemination. Unfortunately, the immune response elicited by RSV normally fails to protect against subsequent exposures to the virus. Despite intense research during the 50 years after the discovery of RSV, scientists are just beginning to understand the mechanisms contributing to pathology and to the inadequate immune response shown by susceptible individuals. Here, we discuss some of the most important advances made in this field that could lead to the development of new prophylactic tools. Copyright © 2012 John Wiley & Sons, Ltd.