This chapter examines harm reduction as a foundational component of street medicine practice for people living unsheltered who use drugs and alcohol. Drawing from clinician interviews and real-world practices across North America, it underscores the importance of patient-led care, trauma-informed communication, and nonjudgmental engagement. The chapter explores the rationale behind common harm reduction strategies—such as needle exchange, supervised consumption sites, naloxone distribution, and safer supply programs—and their role in reducing mortality and morbidity among unsheltered populations. Emphasis is placed on the lived realities of individuals who use substances to cope with trauma, pain, and the chaos of the streets as well as the barriers they face in accessing traditional healthcare due to stigma and criminalization. Substance use assessments are framed not as diagnostic checklists but as relational tools to build trust, understand patient goals, and inform safer care plans. Rather than promoting abstinence, street medicine clinicians focus on meeting patients where they are, supporting self-determined change, and reducing harm at every opportunity. This chapter offers practical guidance and real-world insights for healthcare teams navigating the complexities of addiction care in street-based settings.