INTRODUCTION: Respiratory syncytial virus (RSV) is an important pathogen in infants, children, older adults, and those with comorbidities. Mechanisms involving viral proteins appear to underlie the ability of RSV to evade and modulate host immunity. We aimed to understand virus- and host-dependent factors regulating the development and severity of RSV infection, as related to the prevention and treatment of RSV-associated disease in adults, through a systematic literature review (SLR). METHODS: An SLR was conducted to identify immune mechanisms involved in the protective response to RSV infection in adults, and responses that may contribute to the development of severe disease. Concurrent searches (MEDLINE/Embase) using embase.com identified relevant papers published between 1990 and 19 April 2023. RESULTS: Of 1813 records identified, 113 were selected for review. Inclusion criteria were based on relevant patient populations, outcomes, and study methodologies. RSV is common, recurrent, and associated with high morbidity and mortality in older adults and people with underlying chronic diseases. Immune responses differ between younger and older adults. The approval of effective vaccines may protect older individuals from symptomatic RSV infection. CONCLUSIONS: We established the complexities of RSV immune response, but further research is required to fully understand anti-RSV immunology.