Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infections in infants and older adults. There are several animal models to study RSV infection and test the efficacy of antiviral compounds and vaccines. The lamb model has some advantageous features that contribute to it being one of the best animal models of RSV due to the similarity in size, biology, immune responses, and cellular/structural composition of the respiratory system to infants, the susceptibility to human RSV, and the possibility to investigate multiple approaches and experimental designs. Thus, the lamb model is considered and used as a preclinical model to evaluate the effectiveness and characterize the dosing and mechanisms of newly developed antiviral compounds before they move to human clinical trials. In this chapter, the detailed protocol for the lamb model of RSV infection is explained, including all the assays used to evaluate the severity of infection.