The original antigenic sin (OAS) theory considers the outcome of the first encounter with an antigen. It favors a memory response to the original antigen upon exposure to a similar or related antigen, and includes both positive and negative impacts of past exposure on the memory response to challenge, and, in particular, on vaccine efficacy. This phenomenon is closely linked with imprinting and the hierarchical nature of immune responses to previously encountered antigens. The focus of this commentary centers on the potential role of OAS or immunological imprinting on respiratory syncytial virus memory responses.