Oxidative stress (OS) is a condition caused by an imbalance between reactive oxygen species (ROS) overgeneration and decreased antioxidant defense mechanisms in the cell. OS has become a prominent factor in male reproductive dysfunction as ROS cause damage to sperm DNA, lipids and proteins, alterations to critical sperm structures and signaling pathways, leading to a decreased sperm activity and fertilizing capacity. At the same time, small amounts of ROS play vital roles in events leading to sperm maturation and acquisition of functional activity, which is why a proper oxidative balance is of paramount importance for a proper male fertility. Understanding the physiological and pathological roles of ROS in male reproduction has become an essential pillar of modern andrology; however, numerous questions related to the controversial behavior of ROS in male reproductive cells and tissues still remain unanswered. This chapter aims to summarize current evidence available on the relationships between free radicals, antioxidants and male reproduction and to trigger more scientific interest, particularly with respect to the design of efficient strategies to diagnose or treat male sub-or infertility associated with OS.