This chapter provides a comprehensive exploration of the management of primary hypogonadism in male infertility. Primary hypogonadism, characterized by inadequate testicular function leading to diminished testosterone and sperm production, is a significant factor in male infertility. The text delves into various genetic, congenital, and acquired causes of primary hypogonadism, emphasizing conditions like Klinefelter syndrome, Y chromosome microdeletions, and other chromosomal abnormalities that directly impact sperm production and hormonal balance. A detailed discussion of the diagnostic approaches, including hormonal profiling and testicular biopsies, provides insights into this condition’s clinical evaluation and classification. Therapeutic strategies focus on lifestyle changes, hormone treatments, and advanced assisted reproductive technologies (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), which are crucial for managing severe forms of male infertility linked to NOA. Furthermore, the chapter examines potential new treatments like antioxidant therapy and emerging techniques such as stem cell therapy aimed at restoring normal testicular function. This section not only reflects on the current state of therapy but also considers future directions in the management of primary hypogonadism. The comprehensive overview offers valuable information for clinicians and researchers focusing on the intricacies of male reproductive health and the complex interplay of factors leading to infertility.