Respiratory syncytial virus (RSV) causes seasonal epidemics (winter or wet-season) of serious lower respiratory tract infections in young infants with subsequent increased frequency of recurrent wheezing during early childhood. Palivizumab is a humanized monoclonal antibody that provides immunoprophylaxis against RSV when administered monthly over the RSV season. It significantly reduced hospitalizations in high-risk infants including preterm infants with and without bronchopulmonary dysplasia and infants with hemodynamically significant congenital heart disease. Since its license in 1998, approximately 36 methodologically different economic studies have been performed to prove cost-effectiveness of the product. The majority of cost-effectiveness analyses revealed costs of palivizumab exceeding anticipated savings from reduced RSV hospitalizations. A minority of studies performed cost-effectiveness analyses using incremental cost-effectiveness ratios as costs per quality-adjusted life-year gained. The wide variability in the results of economic studies with estimates ranging from cost savings to incremental costs of a high order of magnitude with its use is discussed, in the light of the continuing burden of RSV disease, the limited treatment modalities, and the continuing research for a vaccine.