Although numerous instruments are used to diagnose mental health disorders and substance use disorders, their accuracy often comes into question when an individual presents with symptoms of both substance use and mental disorders. Hence therapists working with multifarious caseloads must often develop treatment plans before ob­ taining a clear and complete diagnostic picture. This chapter provides an overview of the issues involved in conducting assessments of indi­ viduals presenting with multiple symptoms, and offers ways to obtain the information necessary to develop an effective treatment plan for individuals with a mixed diagnostic picture.