Dysthymic disorder, an insidious and chronic depressive mood disorder that waxes and wanes in intensity over several years, is fairly prevalent in healthcare settings. Although the explicit etiology is unknown, serotonergic dysfunction may be involved. Dysthymia appears to have a high rate of comorbidity, including both psychiatric and medical disorders. The primary care physician should maintain an awareness of this mood disorder, be able to screen efficiently for signs and symptoms, and be able to differentiate major depression from dysthymia. The foundation of treatment is pharmacotherapy, in particular with serotonergic antidepressants, although response is moderate at best. Antidepressants are initiated at low doses and drug trials are conducted for 3-month periods if not precluded by side effects. When reasonably effective, antidepressants should be continued for 2 to 3 years or more. Adjunctive interventions in the treatment of dysthymia are based on comorbid psychiatric or medical conditions. Although dysthymia is an insidious, difficult-to-treat disorder, intervention is worthwhile. Further research may elucidate more effective interventions for this challenging disorder.