The most important recent research leading to future developments in the understanding and treatment of chronic depression are the clinical and epidemiological approaches. 2. The central role of 5HT in depression is emphasized and it seems likely that the maintenance of adequate 5HT neurotransmission is required for the treatment of chronic depression. 3. The role of organic changes in chronic depression must be further explored. 4. The development of novel antidepressants, particularly prophylactic ones, is the most likely way to produce major clinical benefits for this disabled group.