Recurrent Pregnancy Loss (RPL) is an important reproductive health issue affecting 2-5% of couples. The relationship of maternal age to miscarriage correlates with the frequency of aneuploidy in oocytes. Cytogenetic evaluation of sporadic spontaneous abortions has shown that 50-70% is chromosomally abnormal. Because most cases are de novo errors, the risk of an embryo aneuploidy occurring in a subsequent pregnancy is low and the higher the number of miscarriages, the less likely they are to be related to chromosomal abnormalities. The incidence of embryo chromosomal abnormalities is thus lower in women with RPL than in those with sporadic miscarriages. Other possible etiologies have been proposed in case of RPL, either well established such as uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders and high sperm DNA fragmentation levels or even controversial, such as chronic endometritis, inherited thrombophilia and luteal phase deficiency. However, about 50% of the pregnancy loss remains unexplained. Unexplained RPL (URPL) is considered the diagnosis if a complete genetic, anatomic, endocrine and immune evaluation was performed and returned as normal. The chances for a future successful pregnancy in couples with URPL could be as high as 50- 70% and depend mostly on maternal age and the number of previous losses. Nevertheless, multiple pregnancy losses can have a significant psychological toll on affected couples and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This study reviews the predisposing factors and the recommended therapeutic strategies with a focus on the role of preimplantation genetic testing in the management of recurrent pregnancy loss.