Substance use disorders (SUDs) are complex health conditions, which are frequently remitting and relapsing disorders. They can impact many domains of life and require comprehensive knowledge in order to assess in a meaningful way. This chapter conceptualizes people living with SUDs from a holistic, ecological, and trauma-informed perspective and discusses the diagnostic criteria for SUD, including assessment for severity of disorder. It first outlines ways to broadly assess clients at risk for SUD or currently struggling with SUD using an ecological model. Because SUDs are complex and impact many life domains, the chapter includes discussion of health and disability, risk factors, protective factors, and assessments for commonly co-occurring life features, such as trauma, as part of comprehensive SUD assessment practice. This approach aligns with the International Classification of Health, Disability and Functioning model of inclusion of personal and environmental factors known to impact functioning, health, and rehabilitation and recovery efforts.