The gamete membrane fusion test, that uses zona-free hamster oocytes to evaluate the fertilizing ability of human spermatozoa, is being widely used in andrologic laboratories throughout the world. This test evaluates several steps of the reproductive process such as: a) sperm capacitation; b) acrosome reaction; c) gamete membrane fusion; d) sperm chromatin decondensation; e) chromosome condensation; f) egg activation as measured by the cortical granule breakdown and completion of meiosis. This test does not evaluates the sperm transit from the vagina to the site of fertilization nor the sperm passage through the human egg vestments. However, the sperm transit has been partly solved by the use of naturally occurring human cervical mucus to obtain seminal plasma free spermatozoa. This latter technique has greatly increased the diagnostic value of the gamete membrane fusion test. Notwithstanding, the results obtained with this test can vary considerably among the different laboratories, because of variations in the experimental design of the test. These differences can have an important effect upon the attitude the scientist and/or the physician might take in a given case of infertility. The parameters that vary most among the different laboratories are: a) obtention of seminal plasma-free spermatozoa; b) sperm concentrations; c) sperm preincubation time; d) type and concentration of serum albumin used. The original objective of this test was to evaluate the fertilizing ability of spermatozoa of men with problems of infertility. Nowadays is being also used for the assessment of male infertility agents and drugs that might affect the human reproductive function. The correlation found between the results of the gamete membrane fusion test with fertility has resulted in its use in testing the fertilizing ability of bovine and equine spermatozoa.