This article summarizes the current literature regarding azoospermia caused by spermatogenic failure. The causes and genetic contributions to spermatogenic failure are reviewed. Medical therapies including use of hormonal manipulation, whether guided by a specific abnormality or empiric, to induce spermatogenesis are discussed. The role of surgical therapy, including a discussion of varicocelectomy in men with spermatogenic failure, as well as an in-depth review of surgical sperm retrieval with testicular sperm extraction and microdissection testicular sperm extraction, is provided. Finally, future directions of treatment for men with spermatogenic failure are discussed, namely, stem cell and gene therapy.