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Spermatogonial stem cells (SSCs) constitute one of the most important stem cell systems in the adult body. SSCs are unipotent and respond for spermatogenesis in the male as they can only differentiate into sperms within the testicular niche. The long-term culture of SSCs without loss of their properties provides the opportunity to develop therapeutic strategies and re-initiate spermatogenesis for the patients who become infertile after cancer therapy. Moreover, SSCs can be spontaneously reprogrammed into pluripotent germline stem cells (GSCs) similar to embryonic stem cells (ESCs) when they are removed from their in vivo niche and cultured in vitro under specific conditions. The advantage of pluripotent GSCs over induced pluripotent stem cells is that conversion of SSCs into pluripotent GSCs does not require addition of genes using the virus system, which may avoid unpredictable genetic dysfunction. In addition, this may also circumvent ethical problems associated with human ESCs. The ability to generate patient-specific pluripotent GSCs for autologous transplantation provides the opportunity for cell replacement therapy without the need for immunosuppressant. In this review, we discuss the origin, properties and regenerative potential of SSCs. We summarize recent research findings regarding the mechanisms that regulate the self-renewal of SSCs. We believe that studying the biology of SSCs provides us important information to better understand male fertility. Furthermore, we address the contribution of SSCs and pluripotent GSCs to stem cell-based therapy for infertility treatment as well as for organ regeneration in the future.