Suicide remains a leading cause of death in the United States and globally. In this review, epidemiological trends in mortality and suicide risk are presented, with consideration given to the impact of the COVID-19 pandemic. A public health model of suicide prevention with a community and clinical framework, along with advances in scientific discovery, offer new solutions that await widespread implementation. Actionable interventions with evidence for reducing risk for suicidal behavior are presented, including universal and targeted strategies at community, public policy, and clinical levels. Clinical interventions include screening and risk assessment; brief interventions (e.g., safety planning, education, and lethal means counseling) that can be done in primary care, emergency, and behavioral health settings; psychotherapies (cognitive-behavioral, dialectical behavior, mentalization therapy); pharmacotherapy; and systemwide procedures for health care organizations (training, policies, workflow, surveillance of suicide indicators, use of health records for screening, care steps). Suicide prevention strategies must be prioritized and implemented at scale for greatest impact.