Notwithstanding the broad success of in vitro fertilization (IVF), a failure to achieve fertilization still plagues a substantial group of patients, with sperm abnormalities the main culprit. In the 1980s, several micromanipulation procedures were adopted from animal husbandry to facilitate gamete interaction, and this resulted in the development of intracytoplasmic sperm injection (ICSI), a procedure through which an oocyte can be fertilized independently of the morphology and/or motility of the single spermatozoon injected. The procedure was first used in cases of fertilization failure after standard IVF or when an inadequate number of sperm cells were available. The consistency of fertilization independent of the functional quality of the spermatozoon has extended the application of ICSI to immature spermatozoa retrieved surgically from the epididymis and testis. Moreover, the need to denude the oocyte has allowed assessment of the nuclear maturity of the oocyte. ICSI is also preferred in conjunction with preimplantation genetic diagnosis and recently has been used to treat HIV discordant couples, where there is a pressing need to minimize the exposure of the oocyte to a large number of spermatozoa. For all ages and with all the different sperm types used, fertilization after ICSI is at ~70 to 80% and it ensures a clinical pregnancy rate of up to 45%. These results have made ICSI a procedure comparable in popularity with IVF and have minimized the need for couples suffering from all forms of male infertility to resort to adoption or the use of donor sperm.