The fertility potential of patients with nonobstructive azoospermia (NOA) depends on sperm extraction from the tissue sample and then in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI). Unfortunately, there is no consensus regarding predictors that can identify nonobstructive azoospermic men with a potentially high yield at the time of sperm extraction. This article analyzes two competing approaches to these patients: noninvasive and invasive. The noninvasive approach, based on clinical, laboratory, and ultrasonographic investigations, excludes from IVF/ICSI a significant number of patients owing to errors in predicting the presence of sufficient intratesticular spermatozoa. The invasive approach, with available percutaneous or surgical testicular biopsy techniques followed by morphologic examination and or sperm recovery, permits many patients with NOA to receive a favorable prognosis and therapeutic trial. However, the available testicular biopsy techniques are so variable that their performance parameters cannot be adequately compared. As a result, any progress in optimizing these techniques must involve delineation of specific selection criteria for each NOA patient.