Male sexual dysfunction (MSD) is a general term for many different symptoms including erectile dysfunction (ED), failure of sexual intercourse, orgasmic dysfunction and loss of libido. According to statistics, more of 50% of 40–70 years men suffer from varying degrees of MSD. In the last years, significant progresses have been made towards understanding of MSD and the potential pathological mechanisms. Testosterone (T) is involved in every step of the male sexual response, but the occurrence of sexual disorders cannot be related to a decline in T levels. In fact, there are several risk factors such as heart failure, diabetes, hypertension, environmental contaminants, drug toxicity and unhealthy lifestyle involved in pathophysiology of sexual function. Testosterone replacement therapy (TTh) can improve sexual function, erectile function, sexual desire and orgasmic function, particularly in men with hypogonadism and low testosterone levels. The purpose of this chapter is to summarize the current findings of pathogenic factors and the role of testosterone in MSD.