Rapid-response systems (RRSs) are a popular intervention in U.S. hospitals and are supported by accreditors and quality improvement organizations. The purpose of this review is to evaluate the effectiveness and implementation of these systems in acute care settings. A literature search was performed between 1 January 2000 through 30 October 2012 using PubMed, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials. Studies published in any language evaluating outcome changes that occurred after implementing an RRS and differences between groups using and not using an RRS (effectiveness) or describing methods used by RRSs (implementation) were reviewed. A single reviewer (checked by a second reviewer) abstracted data and rated study quality and strength of evidence. Moderate-strength evidence from a high-quality meta-analysis of 18 studies and 26 lower-quality before-and-after studies published after that meta-analysis showed that RRSs are associated with reduced rates of cardiorespiratory arrest outside of the intensive care unit and reduced mortality. Eighteen studies examining facilitators of and barriers to implementation suggested that the rate of use of RRSs could be improved.