Recurrent brief depression (RBD), an affective disorder with a similarly high risk of suicidal behavior as major depression (MD), is characterized by depressive episodes occurring about once a month that last only a few days. The combination of RBD and MD, called combined depression (CD), increases the risk of suicidal behavior enormously. Whereas patients with CD are usually in the care of psychiatrists or neurologists, epidemiological data demonstrate that RBD patients usually see only general practitioners and are not recognized as suffering from an affective disorder. Diagnostic criteria for RBD can be found in the ICD-10 and are helpful in both research and clinical routine. Recurrent brief psychiatric syndromes should be taken into differential diagnostic consideration and are discussed in detail in this review. However, the possibility of prospective diagnostic confirmation of RBD and the way of evaluating drug responses in prophylactic intervention of RBD differ essentially from those in treatment of MD and are more related to clinical procedures used in treating migraine or epilepsy. Differences in the courses of RBD and MD are responsible for different requirements in the design of drug treatment studies. Denial of special methodological needs and highly selected patient samples have probably been responsible for false negative results in double-blind, placebo-controlled treatment studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, no treatment algorithm can be given. Future treatment studies without the limitations of previous studies are clearly needed in the field of RBD.