Experimental studies in laboratory animals have shown that successful conception can be achieved by fertilizing oocytes with immature male germ cells. This gave rise to the concept that immature germ cells recovered from the testes of azoospermic men with maturation arrest may be used for assisted reproduction. However, in contrast to using germ cells recovered from healthy animals, clinical application to the treatment of male sterility is burdened by inherent defects in germ cells attributable to underlying testicular pathology. The recent introduction of in vitro germ cell culture/manipulation techniques makes it possible, in some cases, to overcome the in vivo maturation arrest by allowing an additional meiotic and post-meiotic differentiation and the selective harvesting of cells devoid of apoptosis-related nuclear and cytoplasmic damage. These techniques enabled the first births of normal infants fathered by azoospermic men with maturation arrest at the primary spermatocyte stage and improved the efficacy of assisted reproduction in men with maturation arrest at the round spermatid stage.