The currently characterized chromosomal disorders and gene mutations that cause infertility in humans were reviewed. Of the four arbitrary compartments, genes expressed in the gonad comprise the most common site affected by mutations causing infertility. Clinicians should be aware of the most common causes that have clinical implications: (1) women with a 45,X cell line commonly have cardiac anomalies that may pose a risk for maternal death in pregnancies achieved by donor egg IVF; (2) men with Y-chromosome deletions may produce male offspring with the same deletion, rendering them infertile; (3) CBAVD must be ascertained in men with azoospermia because of the risk for having a child with CF; and (4) some women with premature ovarian failure may be fragile X syndrome carriers, so other family members may be at risk for the full syndrome. In the future, more genes will be identified to cause infertility in humans, which will translate into clinical significance. In select cases, in which the genetic defect is known, it may be possible to use preimplantation genetic diagnosis to screen embryos prior to uterine transfer.