: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infections in infancy. While many infants are infected with RSV, the nature and severity of disease vary among individuals. RSV causes bronchiolitis, pneumonia and asthma exacerbation. However, most children infected with RSV have only mild upper airways disease and may be asymptomatic.: Despite efforts to elucidate mechanisms for the various clinical responses to RSV infection, they remain largely unknown, suggesting that susceptibility and disease are influenced by multiple intrinsic and extrinsic factors. This article reviews the available literature on the field of RSV disease severity and discusses important factors associated to susceptibility and different disease outcome.: The severity of RSV-induced illness is a phenomenon that depends on a variety of graded mechanisms of interaction between the host, virus, and environment. This may lead to differences in intensity of immune response in the lung and different courses of the disease. By characterizing, classifying and grading the affecting factors in high-risk patients versus those who do not fall ill by RSV, we may find therapies or point to disease-limiting medications.