Spermatozoa represent the epitome of terminally differentiated, highly specialized cells. They are transcriptionally and translationally silent and yet manage to undergo a complete functional transformation after they leave the testes, entirely fuelled by post-translational modifications occurring during epididymal maturation and capacitation. The latter have been recognized as biological processes for more than half a century. However, the biochemical mechanisms that drive these events have remained elusive, as have the pathological mechanisms that lead to defective sperm function and infertility. In the past decade the combined power of advanced proteomics, biochemistry, and functional genomics has permitted an unprecedented improvement in our understanding of sperm cell biology. We can also predict that a systems-biology approach, in concert with the new tools provided by the 'omics' revolution, will lead to dramatic gains in our understanding in the near future. As a result of such advances, insights will be generated that should ultimately lead to significant improvements in our capacity to diagnose and treat the infertile male.