With infertile couples, one third of cases can be due to a male factor. It is important to have a comprehensive yet efficient approach to identifying potential causes for appropriate counseling and treatment. We combined the experience of a urologist and a gynecologist, both fertility subspecialists, and reviewed current literature on the investigation of male infertility. A history and physical examination supplemented by relevant investigations will help unravel any significant diseases that can be associated with male subfertility or any conditions that may be transmitted to future offspring. Semen analysis is a common, convenient measure of assessing the male. It should precede any invasive tests of the female. While reference values are important in standardization, the current trend in using sperm morphology alone in predicting male fertility remains problematic. Overreliance on this reference can lead to misdiagnosis and unnecessary invasive treatment with intracytoplasmic sperm injection (ICSI). In those who have no identifiable or correctable causes, ICSI provides new hope for couples with male infertility who, in the past, could only choose among therapeutic donor insemination, adoption or voluntary childlessness. With increasing application of these assisted reproductive technologies, it is important to rule out genetic causes, such as cystic fibrosis, and to provide appropriate genetic counseling before embarking on these invasive and costly procedures.