In the literature, a distinction between patients with secondary recurrent miscarriage (RM), defined as RM after a previous birth, and primary RM with no preceeding birth is often not made. In this review we point out that there are fundamental epidemiological, clinical and paraclinical differences between these two major subsets of RM patients. There are indications that most cases of secondary RM are caused by an abnormal reaction of the adaptive immune system against the fetus or trophoblast whereas primary RM has a more mixed etiology with many cases caused by disturbances in the coagulation pathways or in the innate immune system. These differences in pathogenesis are reflected in the different responses of the two patient subsets to immunotherapy: many primary RM patients benefit from allogeneic lymphocyte immunization whereas most patients with secondary RM benefit from intravenous immunoglobulin. It is important in future case-control studies or trials of therapy clearly to report the main outcome measures separately for patients with primary and secondary RM, respectively.