Drugs and xenobiotics can compromise reproductive function by impairing gamete physiology and thereby blocking fertilization, or by damaging gamete DNA or chromatin and thereby causing pregnancy failure or birth defects. Standard measures of gamete integrity, such as morphology, motility (sperm), or fertilizing ability, while useful in identifying and characterizing adverse effects, may not identify genetic damage in the gametes. To better assess gamete integrity, methods capable of detecting DNA or chromosomal damage in individual sperm or egg cells are needed. The report summarizes recent advances in in vitro technologies for assessing both the pathophysiologic and genetic integrity of gametes with emphasis on the latter.