As injection drug use increases, needle exchange programs (NEPs) are one method of reducing infectious disease transmission and improving health outcomes for this population. The purpose of this paper is to examine the effectiveness of NEPs. A comprehensive review of the literature was conducted to investigate the study aim. Specific inclusion criteria included 1) studies published in English, 2) studies examining needle exchange, 3) studies conducted in the United States, 4) studies conducted between 2007 and 2017, and 5) studies focusing on injection drug users. Exclusion criteria are also included. A total of 12 studies examining NEPs were found. The research team evaluated all 12 studies and emergent themes included: (1) reduction in risk behaviors, (2) sex differences in use and behaviors, (3) overall perceptions of needle/syringe exchange programs, and (4) methodological flaws and implementation. This review indicates that NEPs are effective in reducing infectious disease and improving health outcomes. Lack of consistent methods in NEP research may be an issue. In addition, community and health professional attitudes may need to be addressed to enhance effectiveness. Programs and initiatives aimed at educating community members and others may be warranted.