Women with unexplained recurrent pregnancy loss (RPL) represent a highly heterogeneous group of patients. Past studies have investigated systemic endocrine and immunologic mechanisms as potential causes for pregnancy loss in unexplained RPL, while exciting new work has focused on spermatozoal, embryonic, and endometrial characteristics to explain the regulation of implantation and subsequent pregnancy loss. In the clinical and research context, stratification of women with unexplained RPL according to whether they have a high probability of pathologic status will help select women who are most appropriate for further investigation and potential future treatment.