The exact physiopathologic effect of testicular varicocele on male fertility is not defined yet. The detrimental role of the varicocele in fertility is supported by the presence of a higher frequency of affected men among the infertile population. However, the mechanism/s by which a varicocele impairs sperm production, structure and function, is not known. In spite of active interest, our understanding of the human male gamete ultrastructural molecular organisation is still incomplete and therefore our knowledge of the sperm molecular anatomy is very limited. The presence of steroid binding sites on human spermatozoa has been evidenced since the 1970s, and afterwards, spermatozoa physiology was linked to the action of different steroids. The presence of steroid/steroid receptor systems was demonstrated in mature spermatozoa as membrane but also as nuclear conventional receptors, suggesting that both systemic and local steroids, through sperm receptors, may influence male fertility. From new data, it emerges that varicocele may induce damage in the male gamete at molecular level, opening a new chapter in the already multifactorial pathophysiology of the varicocele, complicating this issue. In sperm from varicocele, a decreased expression of steroid receptors and a consequent reduced responsiveness to steroids may represent a mechanism involved in the physiopathology of varicocele. Therefore, the modulation of these nuclear receptors pave the way for novel therapeutic opportunities in the treatment of the male pathologies related to human reproduction. The purpose of this review is to gain new insight into the physiopathology of varicocele and to study its impact on human sperm molecular anatomy.