People with co-occurring physical and mental conditions represent a significant and costly portion of the population. This synthesis examines the evidence on physical and mental comorbidity including its prevalence, origins and models for effective treatment. Key findings include: Comorbidity is the rule rather than the exception. More than 68 percent of adults with a mental disorder had at least one medical condition. Comorbidity is associated with elevated symptom burden, functional impairment, decreased length and quality of life and increased costs. The pathways causing comorbidity is complex and bidirectional. Medical disorders may lead to mental disorders, mental conditions may place a person at risk for certain medical disorders, and mental and medical disorders may share common risk factors. Collaborative care models that use a multidisciplinary team have been shown to provide effective treatment for persons with comorbid physical and mental conditions. The most effective treatment models, however, are not in widespread use.