The aim of this review was to assess critically the importance of the frequency, quantity and quality of retrograde menstruation and its relationship to peritoneal inflammation. The basis was the current evidence in women and in baboons supporting the Sampson hypothesis that retrograde menstruation is a key factor in the pathogenesis of endometriosis. It is not proven that retrograde menstruation is a universal phenomenon occurring similarly in women with and without endometriosis. A more thorough understanding of the physiological, cytological and immunological events in peritoneal fluid, peritoneum, endometrium and uterus during menstruation in women with and without endometriosis is critical in order to understand the pathogenesis of this enigmatic disease.