The advent of assisted reproductive technologies, particularly intracytoplasmic sperm injection (ICSI), has revolutionized the treatment of male-factor infertility. However, there are many unanswered questions regarding the safety of these techniques. These safety concerns are relevant because 1) these technologies often bypass the barriers to natural selection; 2) infertile men, particularly those with severe male-factor infertility, possess substantially more sperm DNA damage than do fertile men; and 3) experimentally, sperm DNA damage has been shown to adversely affect the developing embryo. This review discusses the etiology of sperm DNA damage, describes the individual tests of sperm DNA damage, and explores the relationship between sperm DNA damage and pregnancy outcomes. Based on a systematic review of the literature, sperm DNA damage is associated with lower natural, intrauterine insemination (IUI), and in vitro fertilization (IVF) pregnancy rates, but not with ICSI pregnancy rates. The literature also suggests that that sperm DNA damage is associated with an increased risk of pregnancy loss in those couples undergoing IVF or ICSI. Nonetheless, the true clinical utility of sperm DNA damage tests remains to be established, because the available studies are small and few in number and the study characteristics are heterogeneous. Although current data suggest that impaired sperm DNA integrity may have the greatest effect on IUI pregnancy rates and pregnancy loss by IVF and ICSI, further prospective studies are needed before testing should become a routine part of patient management.