The definition, recognition, and management of chronic depression are briefly reviewed. An ongoing prospective study of the long term (5-15 years) use of doxepin indicates that this tricyclic antidepressant is feasible, efficacious, and safe in the treatment of this population. Advantages of doxepin therapy include its lack of adverse interactions with prescription and non-prescription drugs taken by these patients and the high degree of safety seen in patients with concomitant cardiovascular and other physical disorders. Thus, doxepin appears to be an excellent choice in the long-term maintenance outpatient treatment of chronic depression.