Male infertility is a multifaceted disease where genetic, epigenetic and environmental factors all contribute to the development of the phenotype. In recent years, there has been an increasing concern about a decline in reproductive health, paralleled by an increase in demand for infertility treatments. This calls for a detailed and thorough understanding of normal and aberrant testicular function and the environmental influences on the establishment and integrity of the male germ cell. This is crucial for understanding the complex pathophysiology of male infertility and eventual success of Assisted Reproductive Technologies.