Among other factors, chromosomal abnormalities that originate from gametogenesis and preimplantation embryonic development are thought to be one of the major contributing factors for early embryonic death and failure of pregnancy. However, so far, no non-invasive technique exists that allows the detection of the chromosomal complement of an oocyte or a developing embryo as a whole. Rather, by removing polar bodies/blastomeres, recent developments on preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) have paved the way to detect and possibly eliminate the majority of chromosomally abnormal embryos, thereby increasing the chance of a healthy pregnancy. This article summarizes the origin and impact of chromosomal abnormalities on human reproduction in cases with repeated implantation failure (RIF) and unexplained recurrent miscarriage. It also discusses recent advances regarding the possible benefits of PGD-AS in such cases.