Respiratory syncytial virus (RSV) is a significant cause of illness in children< 2 years of age, resulting in 2%–3% of infected children requiring hospitalization [1]. Globally, RSV was estimated in 2005 to have caused approximately 34 million cases of acute lower respiratory tract (LRT) illness and 66 000–199 000 deaths in children, with 99% of these deaths occurring in developing countries [2]. With the development of more sensitive diagnostic techniques, particularly polymerase chain reaction, the recognition of high disease burden and associated mortality in immunocompromised hosts and in older adults has increased [3–5]. Despite the disease burden, specific antiviral treatment for RSV disease remains an unmet medical need. Here we summarize problems and progress in achieving successful therapeutic interventions.