Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. More than 50 years after its discovery, and despite relentless attempts to identify pharmacological therapies to improve the clinical course and outcomes of this disease, the most effective therapy remains supportive care. Although the quest for a safe and effective vaccine remains unsuccessful, pediatricians practicing during the past decade have been able to protect at least the more vulnerable patients with safe and effective passive prophylaxis. This review summarizes the history, microbiology, epidemiology, pathophysiology, and clinical manifestations of this infection in order to provide the reader with the background information necessary to fully appreciate the many challenges presented by the clinical management of young children with bronchiolitis. The last part of this article attempts an evidence-based review of the pharmacologic strategies currently available and those being evaluated, intentionally omitting highly experimental approaches not yet tested in clinical trials and, therefore, not likely to become available in the foreseeable future. Pediatr Pulmonol. 2011; 46:324–347. © 2010 Wiley-Liss, Inc.