Harm reduction is an evolving prevention and practice model for helping professionals that views any positive change in undesired, problematic, or risky target behaviors as a successful outcome. Harm reduction represents a significant shift away from the absolute, all-or-nothing expectations of traditional, medical-model-based approaches commonly employed in health and human service programs and interventions. In contrast to programs, practices, and policies based on behavioral models that seek to eliminate risk altogether, harm reduction strategies focus on minimizing the potential harm that results from risky behaviors in a person’s life. In recent decades, in response to growing concerns about harmful outcomes of drug use, substance abuse, and chemical dependency, harm reduction strategies have been used to address rising rates of human immunodeficiency virus (HIV) and hepatitis infection, overdose deaths, and other health concerns among drug users, particularly those who inject. Syringe exchange programs, safe injection/supervised consumption rooms, narcotic substitution, and other innovative applications of harm reduction principles have emerged, and evidence of the success of such efforts is mounting. While many of these activities and interventions exist in the United States, US officials have been reluctant to fully embrace harm reduction. Resistance by politicians, policymakers, and funders has been common. In contrast, harm reduction has been adopted as a central theme of national drug policies in many countries and international entities around the world. Furthermore, although originating in the field of chemical dependency, the philosophy and strategies of harm reduction are pertinent to a wide variety of complex social welfare and public health issues, including alcohol and tobacco use, homelessness, sexual behavior, sex work/prostitution, sex offender treatment, domestic violence, divorce law, and compulsive behaviors such as gambling and computer use. Nonprofit and nongovernment organizations now exist in the United States and elsewhere and provide services, information, and advocacy based on harm reduction.