This chapter provides practical guidance for prescribing psychotropic medications to individuals living unsheltered with trimorbidity, emphasizing a harm reduction framework. It underscores the importance of informed consent, bodily autonomy, and patient-led decision-making. The chapter details the risks and benefits of various psychotropic medications—including antipsychotics, antidepressants, mood stabilizers, and medications to treat ADHD—in the context of street environments, highlighting factors such as sedation, overdose risk, and storage challenges. Long-acting injectables are recommended when feasible to improve outcomes and reduce loss of medication due to theft and encampment sweeps. Special sections address how to manage side effects like extrapyramidal symptoms, sexual side effects, and seizure risk, and how to adapt dosing schedules for street conditions. The use of genetic testing is briefly discussed as a tool to guide treatment for patients with complex medication histories. By equipping clinicians with street-adapted strategies and risk assessments, this chapter aims to improve psychiatric care delivery to unsheltered populations.