The challenging nature of recurrent pregnancy loss (RPL) is multifactorial, but largely begins with determining who meets diagnostic criteria for RPL as definitions vary and frequently change. Many patients seek obstetrical intervention after losses, even if they do not meet the criteria for RPL, and even those strictly meeting criteria often present a conundrum as to the etiology of their condition. The contribution of hereditary thrombophilia to RPL, the impact of each disorder on the clotting cascade, available evidence regarding pregnancy outcomes, and current recommendations for evaluation and treatment is presented.