Recurrent pregnancy loss (RPL), which occurs in 0.5%-1% of total pregnancies, is usually defined as three or more consecutive spontaneous abortions before 20 weeks of gestation. Although an immunology-based etiology underlying unexplained RPL has been demonstrated, the exact molecular mechanisms are still poorly understood. Recent studies using transcriptomics and proteomics have implicated several factors. Here, we review the key possible mechanisms, in particular immunological abnormalities and thrombophilic aberration, that might underlie RPL. Taken together, these findings provide insight into the development of effective therapeutics for RPL.