Innovative techniques for testis biopsy interpretation continues to generate new and meaningful information regarding the pathophysiology in the infertile male. This chapter outlines the relevant histologic features of both abnormal and normal testis biopsies. It reviews existing, new, and promising technologies that are being applied to testis biopsy. A by-product of the refinement of needle biopsy techniques in the testis is fine-needle aspiration (FNA) for systematic mapping of sites of active spermatogenesis. Cytological assessment of biopsy or aspirate specimens can be performed in several ways. Basement membrane hyalinization refers to concentric thickening of the inner basement membrane, as evidenced by deposition of hyaline. The germinal epithelium of the seminiferous tubule is composed of germ cells in various stages of development and Sertoli cells. The therapeutic nature of the testis biopsy depends on the ability to identify mature spermatids that might be appropriate for IVF/intracytoplasmic sperm injection (ICSI).