The decline of human fecundability stems from compromised quality and reduced quantity of gametes. The age-related female infertility and spermatogenic failure have been the major obstacle to overcome in ART with only limited success unless donated gametes are used. I review the different approaches to manufacturing and regenerating gametes. Attempts of nuclear transplantation for preventing oocyte aneuploidy thereby enhancing the developmental competence or for inducing haploidization of somatic cell nuclei aiming to generate oocytes and spermatozoa are explored by highlighting advantages and limitations of these strategies. In addition, approaches to differentiate precursor cells or pluripotent stem cells to their progenies or mature gametes are revisited. Finally, I also report preliminary data on enhancing the reproductive performance of a single spermatozoon by male genome cloning utilizing micromanipulation techniques.