OBJECTIVE: This systematic review focused on randomized controlled trials (RCTs) with physicians and nurses that tested interventions designed to improve their mental health, well-being, physical health, and lifestyle behaviors. DATA SOURCE: A systematic search of electronic databases from 2008 to May 2018 included PubMed, CINAHL, PsycINFO, SPORTDiscus, and the Cochrane Library. STUDY INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria included an RCT design, samples of physicians and/or nurses, and publication year 2008 or later with outcomes targeting mental health, well-being/resiliency, healthy lifestyle behaviors, and/or physical health. Exclusion criteria included studies with a focus on burnout without measures of mood, resiliency, mindfulness, or stress; primary focus on an area other than health promotion; and non-English papers. DATA EXTRACTION: Quantitative and qualitative data were extracted from each study by 2 independent researchers using a standardized template created in Covidence. DATA SYNTHESIS: Although meta-analytic pooling across all studies was desired, a wide array of outcome measures made quantitative pooling unsuitable. Therefore, effect sizes were calculated and a mini meta-analysis was completed. RESULTS: Twenty-nine studies (N = 2708 participants) met the inclusion criteria. Results indicated that mindfulness and cognitive-behavioral therapy-based interventions are effective in reducing stress, anxiety, and depression. Brief interventions that incorporate deep breathing and gratitude may be beneficial. Visual triggers, pedometers, and health coaching with texting increased physical activity. CONCLUSION: Healthcare systems must promote the health and well-being of physicians and nurses with evidence-based interventions to improve population health and enhance the quality and safety of the care that is delivered.