Respiratory syncytial virus (RSV) is the major respiratory pathogen in infants and young children. Ribavirin is the only antiviral agent approved for the treatment of RSV infections, but its efficacy has remained controversial. In the past few years several compounds have been described that in vitro exhibit marked activity against RSV at a 50% effective concentration that is significantly lower, and with a selectivity index that is significantly higher, than that of ribavirin. Among the most potent and selective RSV inhibitors are various polyanionic substances (polysulfates, polysulfonates and polyoxometalates), EICAR (an IMP dehydrogenase inhibitor), pyrazofurin (an OMP decarboxylase inhibitor) and cyclopentenylcytosine (Ce-Cyd, a CTP synthetase inhibitor). These compounds should be further explored for their therapeutic potential in the treatment of RSV infections, following systemic or, preferably, topical administration (i.e. as an aerosol), as topical application may better mimic the potency and selectivity exhibited in vitro by these compounds.