Development in ART has been remarkable in the last decades. Several medical conditions affecting the male fertility status are now treated by ART, especially by the combination of in vitro fertilization and intracytoplasmic sperm injection. ICSI is now the treatment of choice of most untreatable causes of male infertility, including immunologic infertility, severe oligozoospermia and azoospermia. Sperm retrieval techniques have been optimized and microsurgery offers the possibility of collecting testicular spermatozoa even in the most difficult cases of non-obstructive azoospermia. Nonetheless, the reproductive potential of sperm from men with defective spermatogenesis is decreased in ART and such treatment modalities may carry an increased risk of transmitting genetic and epigenetic defect to the embryo. Efforts should be made to improve the male health status prior to embarking on ART because current evidence suggests that fertility optimization may improve treatment outcomes. Moreover, laboratory management of male infertility cases requires special attention. Spermatozoa collected from men with severely impaired spermatogenesis are often compromised and fragile. Adherence to state of the art laboratory techniques and quality control are recommended to avoid jeopardizing sperm fertilizing potential and the chances of achieving a live birth. In this study, we present and critically review our 10-year experience in the management of severe male factor infertility using ART.