Abstract-Introduction:Premenstrual syndrome is a psychoneuroendocrine disorder of unknown etiology. Even after > 80 years of its 1st description, its definition, presenting patterns , diagnostic plan and treatment modalities are surrounded by many questions and controversies. This results in a large number of studies with different criteria's and methodologies so that their results are not comparable. Objective : To descries variability in opinions about PMS and highlight problems encountered in designing and conduct of clinical trials of various drugs in premenstrual syndrome. Method : The literature available in journals since inception of the term Premenstrual syndrome was reviewed. Variability in opinions of different workers regarding definition of PMS, days of premenstruum, diagnostic parameters was recorded and analysed. The methodological constraints in clinical trials of PMS due to lack of consensus among workers are mentioned and some corrective measures are suggested. Results : There is no consensus among workers regarding different aspects of premenstrual syndrome resulting in difficulties in designing and conduct of clinical trials in PMS. Conclusion :The authorities and organizations involved in research on PMS must frame standard guidelines for acceptable criteria and trial designs. So that comparative study of different trials becomes possible. Large multicentric trials in identical groups of population at same period of time by uniformly trained investigators are another alternative. Further research to elucidate exact etiopathogenesis and treatment guidelines is essential.