There is accumulating evidence linking sperm chromatin damage to poor reproductive outcome. The chromatin damage is associated to sperm anomalies that manifest themselves as breaks in the sperm nuclear DNA, aberrant ratios of protamine and histones in the chromatin, and the presence of apoptotic marker proteins in the ejaculated spermatozoa. This chapter examines the mechanisms involved in generating chromatin damage during spermatogenesis in the human, the techniques used to test sperm chromatin and how they may affect reproductive outcome, and how to reduce the risk of using spermatozoa with chromatin damage.