Couples referred for preimplantation genetic diagnosis (PGD) are known to be at genetic risk due to an affected family member or the birth of an affected child. PGD involves three stages: IVF, embryo biopsy and single cell diagnosis. Polymerase chain reaction (PCR) is used for the diagnosis of single gene defects such as cystic fibrosis, screening of specific diagnosis of X-linked diseases and the triplet repeats disorders such as myotonic dystrophy. For PGD patients, especially those carrying fragile X syndrome, a test of ovarian reserve is recommended. The embryo biopsies discussed in this chapter are: polar body biopsy, cleavage stage biopsy, blastocyst biopsy. The chapter lists out single gene disorders for which successful PGD protocols have been reported. Fluorescent in situ hybridization (FISH) determines the number of copies of a particular chromosome or region of a chromosome when it is difficult or impossible to obtain good quality metaphase preparations.