The diagnosis of male infertility is a rapidly developing field of investigation. The traditional descriptive approach to semen analysis is still at the heart of the diagnostic workup of male patients and important advances have been made in the standardization of the procedures used to construct the conventional semen profile, as embodied in the WHO handbook. Significant improvements have also been made in the techniques used to assess the quality of sperm motility. While this was once an entirely subjective exercise, the introduction of CASA systems to take objective measurements of the trajectories of human spermatozoa has revolutionized this form of analysis. The speed and accuracy of such systems has permitted detailed analyses of the relationships between sperm movement and sperm function, which has greatly enhanced the diagnostic power of this form of descriptive analysis. Notwithstanding the importance of the descriptive approach to semen analysis, it has also been recognized that to achieve an accurate diagnosis of male infertility such criteria should be supplemented with assays designed to reveal the functional competence of the spermatozoa. Bioassays have therefore been developed to measure such functions as the penetration of cervical mucus, sperm-zona interaction, the acrosome reaction, and sperm-oocyte fusion. All of these assays have been shown to generate information predictive of the fertilizing potential of human spermatozoa in vivo and in vitro. Despite their diagnostic value, the time, expense, and expertise required to run such functional assays has meant that they have not been widely used by infertility specialists. These functional assays are of value, however, in fundamental studies designed to elucidate the biochemical basis of defective sperm function. The first fruits of this research effort are now beginning to appear in the identification of a number of cytoplasmic markers for defective sperm function and the realization that lipid peroxidation plays a key role in the etiology of male infertility. In the wake of these fundamental studies will flow a new generation of biochemical tests for the diagnosis of defective sperm function and, it is hoped, the development of rational therapies with which to treat this condition.