Recurrent brief depressive disorder (RBD) is a well-defined and significantly prevalent affective disorder with an increased risk of suicidal behavior and significant clinical impairment in the community and general practice. RBD is characterized by depressive episodes occurring at least once a month and lasting for only a few days. The lifetime co-occurrence of both RBD and major depressive disorder (MDD), called combined depression (CD), increases substantially the risk for suicide attempts, even more than is known for "pure" MDD. Diagnostic criteria for RBD can be found in the ICD-10 and DSM-IV and are helpful in both, research and clinical routine. Furthermore, several methodological issues are covered in this paper, which make clinical diagnostic and drug response evaluation of RBD very different from MDD. However, clinical procedures rather bear a resemblance to those used in the treatment of migraine or epilepsy. Formal differences in the course of RBD and MDD create different needs concerning the design of drug treatment studies. Absence of special methodological requirements and highly selected patient samples has 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, it is still not possible to deduce a treatment algorithm for RBD to date. Obviously, future treatment studies without the limitations of previous studies are clearly required for RBD.