The introduction of intracytoplasmic sperm injection (ICSI) provides new hope for many couples suffering from the most untreatable forms of male infertility as ICSI can also be successfully performed using epididymal or testicular spermatozoa. Testicular spermatozoa may be recovered from testicular tissue in every patient with excretory azoospermia, but also in about half of patients with secretory azoospermia. The strongest parameter to predict successful testicular sperm recovery is histopathological examination of a testicular biopsy, especially in patients with some form of germ-cell aplasia. Even in our series of Klinefelter patients, testicular sperm were recovered in eight out of 15 patients and after seven ICSI cycles combined with preimplantation diagnosis, two singletons were born. Less invasive techniques such as percutaneous fine-needle aspiration have been introduced and may yield comparable success rates in patients with normal testicular function. The high fertilization rates after testicular sperm recovery and ICSI and the favourable implantation rates may therefore render microsurgical epididymal sperm aspiration (MESA) obsolete in the future for patients with normal spermatogenesis. Besides, the use of cryopreserved testicular spermatozoa may become an alternative to repeated surgery for obtaining testicular tissue for subsequent ICSI treatment cycles.