Respiratory syncytial virus (RSV) was first isolated from infants by Chanock and colleagues in 1957. However, control of this ubiquitous agent has yet to be achieved. RSV is recognized as the primary cause of hospitalization for acute lower respiratory tract illness (LRTI) among infants worldwide. Among children <5 years old, annual hospitalization rates in the United States (US) is 3/1000 children, and rates in Canada and European countries are similar. In the US the hospitalization rate is 3 times higher than that from influenza or parainfluenza viral infections. Much less appreciated is the clinical and economic burden from RSV outpatients, as few have specific diagnostic testing. Nevertheless, RSV in the US is estimated to cause 1 of 334 hospitalizations, 1 of 38 emergency department visits, but 1 of 13 private practice visits. These outpatient children tend to have moderate to severe illness with approximately three-fourths manifesting labored respirations. RSV burden among outpatients, therefore, is considerable both in size and severity. The global burden of RSV infection is unknown as few studies are from developing countries. Estimates indicate about one-fourth of all acute LRTI occur among children <5 years, and the greatest burden is among children in developing countries. Currently the only approved means of RSV prophylaxis is passive immunization with humanized F protein monoclonal antibody. Such prophylaxis, however, has limited availability, is expensive, and is recommended only for infants most at risk for severe RSV disease. Only widespread immunization of children is likely to diminish the current burden of RSV infection.