Mental stress has an enormous impact on physical health. This impact commonly manifests as headache, muscle tension, acne, peptic ulcer disease, or a compromised immune system. Stress is also associated with more serious adverse effects, such as cardiovascular disease and exacerbations of rheumatoid arthritis and systemic lupus erythematosus. As these effects are far-reaching, it is important for primary care physicians to identify and manage the symptoms of mental stress in their patients. This is increasingly possible with office-based mental stress testing, which uses cardiovascular markers to identify patients who are overresponders to mental stress, and, thus, at risk for stress-induced disorders. Mental stress in this population can be managed with nonpharmacologic and pharmacologic interventions to improve patients' responses to stress and decrease morbidity and mortality associated with this condition.