BACKGROUND The rapid response system (RRS) was designed to identify and intervene on patients exhibiting clinical deterioration in the non-critical-care setting but is not always effectively activated by nurses, leading to adverse patient outcomes. OBJECTIVE The objective of this systematic review was to explore nurses' perceived barriers to RRS activation in the acute adult inpatient setting. METHODS A systematic review was completed utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist. Six different search terms were used in the following electronic databases: Academic Search Premier, the Cumulative Index to Nursing and Allied Health Literature, Healthsource: Nursing/Academic Edition, MEDLINE, and PubMed. Limiters applied to search methods included years 2007 to current, full text, scholarly (peer reviewed), and English language. This review was further limited to quantitative studies in the adult inpatient setting. RESULTS The initial electronic database search yielded 149 articles. After duplicate exclusion, 87 article abstracts were reviewed for inclusion and eligibility, and a total of 8 articles were used for this systematic review. Themes to nurses' perceived barriers to RRS activation include RRS activator-responder interaction, physician influence, nurse education, and nurse experience. CONCLUSIONS Nurses play a vital role in patient care by providing continuous surveillance and are the frontline for early detection including prompt intervention should a patient's condition deteriorate. Inconsistent RRS activation has been associated with negative patient outcomes. Exploring nurses' perceived barriers to RRS activation may contribute to interventions that lead to nurses appropriately activating the RRS and potentially decreasing adverse patient outcomes.