Chronic illnesses affect nearly half of US adults, and nearly 30% of these patients suffer from a co-occurring mental health problem. Despite the high prevalence of comorbidity, existing treatments and service delivery approaches largely reflect fragmented, disease-specific care. Acceptance and commitment therapy (ACT) is a transdiagnostic behavioral intervention that is effective at promoting health behavior change and reducing distress among patients. ACT targets avoidance, helps individuals accept what cannot be changed with greater equanimity, and fosters the development of skills to engage more fully in meaningful life activities. Notably, ACT has been successfully implemented in hospitals, primary care, and specialty care settings.