There is a male factor involved in up to half of all infertile couples. Potential causes of male factor infertility are many and require thorough evaluation for their accurate elucidation. A complete medical history in conjunction with a focused examination can allow for an appropriate choice of laboratory and imaging studies. The semen analysis is a crucial first step, but it is by no means sufficient to determine cause or dictate therapy. A systematic approach is necessary to help guide the evaluation and exclude less likely causes. The causes discussed within this article are broad, and the prognosis for any given couple depends, in large part, on the cause of the infertility. Without a firm understanding of the genetics, anatomy, physiology, and their interactions necessary to permit full functioning of the male reproductive system, the evaluation becomes an inefficient exercise that often fails to elucidate the precise cause of infertility. Treatment success relies not just on a clinical diagnosis but on a determination of the cause of the male factor infertility. Therefore, couples with a component of male factor infertility need a systematic evaluation directed at the male partner to maximize their reproductive potential.