Nonobstructive azoospermia (NOA) remains a challenging condition in reproductive medicine to manage. The genetic basis of NOA related to partial deletions of the Y-chromosome has been intensely investigated. Such information is of prognostic value and allows more insightful genetic counseling of couples who opt for assisted reproductive technology. Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection has allowed many men with NOA to father their own biologic children. Although studies in the current literature support open testicular biopsy as the most reliable method to obtain testicular sperm, less invasive techniques such as testicular fine-needle aspiration and percutaneous needle biopsy are feasible alternatives in selected groups of patients. Measures to improve the efficacy of TESE, including the application of microsurgical techniques, are addressed. Other recent developments related to the management of NOA reviewed include processing of testicular tissue, cryopreservation of retrieved spermatozoa, in-vitro maturation of germ cells and microinjection of immature spermatogenic precursor cells.