Preimplantation genetic diagnosis (PGD) refers to a procedure to genetically analyze embryos prior to implantation, in order to prevent the occurrence of specific inherited disorders before conception and improve the outcome of high-risk pregnancy with genetic disorders. In recent years, with the advance of molecular biology techniques, more and more genetic diseases have been elucidated, and PGD has been gradually expanding its scope and applications. New technologies, such as microarray comparative genomic hybridization (array CGH), are developed to improve the accuracy of diagnosis. However, the safety of this procedure has aroused great attention. In this article, authors will review the safety of zona opening procedures, different biopsy procedures at different stages, and removal of one or two cells from cleavage-stage embryos. The reliability of genetic analysis technologies will be discussed as well.