OBJECTIVE: No widely accepted clinical guidelines, and scant directly applicable pragmatic research, are available to guide the prescription of psychiatric medications in low-threshold outpatient settings, such as street outreach, urgent care, and crisis care, as well as walk-in, shelter, and bridge and transition clinics. Providers frequently prescribe medications in these settings without patients having firm psychiatric diagnoses and without medical records to guide clinical decision making. Persons who receive medications in these settings often seek help voluntarily and intermittently for mental illness symptoms. However, because of structural and individual factors, such patients may not engage in longitudinal outpatient psychiatric care. The authors reviewed the literature on psychiatric medication prescribing in low-threshold settings and offer clinical considerations for such prescribing. METHODS: The authors conducted a rapid literature review (N=2,215 abstracts), which was augmented with up-to-date clinical prescribing literature, the authors collective clinical experience, and DSM-5 section II diagnostic criteria to provide considerations for prescribing medications in low-threshold settings. RESULTS: For individuals for whom diagnostic uncertainty is prominent, a symptom-based diagnostic and treatment approach may be best suited to weigh the risks and benefits of medication use in low-threshold settings. Practical considerations for treating patients with clinical presentations of psychosis and trauma, as well as mood, anxiety, and substance use disorders, in low-threshold settings are discussed. CONCLUSIONS: An urgent need exists to invest in pragmatic research and guideline development to delineate best-practice prescribing in low-threshold settings.