Infertility has become a public health problem affecting approximately 1 in 10 couples globally. Male infertility alone contributes to nearly 60% of the problem and has turned out to be a key health concern, the incidence of male infertility ranges from 2.5% to 12% across different regions around the world. The impaired spermatogenesis and functions can be associated with factors which act at pre-testicular level, at the level of testis or at post-testicular level. This chapter covers the pretesticular causes, hypogonadotropic hypogonadism, coital disorders, testicular causes, genetic causes, inflammation, effect on the male reproductive tract, reactive oxygen species, and factors that help in prognosticating male infertility. Understanding the etiology and pathogenesis of male infertility will help clinicians in achieving the right diagnosis and offering appropriate counseling to the patient about the pathology and treatment options. Multidisciplinary input between reproductive medicine specialists, endocrinologists and surgeons may be required in some cases to optimize treatment.