Patients with co-occurring disorders (CODs) have a substance use disorder (SUD) and at least one other mental health diagnosis. Many patients with a non-SUD mental health diagnosis also have an SUD, whereas most patients with SUDs have other co-occurring psychiatric disorders. Recognition is growing regarding the importance of identifying and treating CODs. This article reviews the magnitude of CODs, theories by which CODs develop, treatment options for CODs (including psychotherapeutic and psychopharmacologic interventions), current treatment initiatives for CODs, and ways to prevent CODs. Although research on CODs is providing direction and hope for treatment, many more questions than answers remain regarding these challenging conditions.