The fusion of male- and female-derived gametes initiates the phenomenal process of producing a highly complex mammalian organism. Successful reproduction is so important that mammals invoke a battery of protective mechanisms for the germ cell lineages that function to maximize genetic integrity while still allowing genetic diversity and adaptation. Protective mechanisms likely include, but are not limited to, robust DNA repair to safeguard genetic integrity and apoptosis to remove cells with intolerable levels of DNA damage. Analyses of spontaneous mutant frequencies are generally consistent with germline DNA being stringently maintained relative to somatic tissues. Despite the rigorous protection afforded germ cells, genetic integrity is observed to decline with increased maternal and paternal age. It is not yet clear whether cells in the germ line truly age or whether other processes decline or become dysfunctional with age. For example, in a younger animal, the differentiation and/or utilization of germ cells with lower genetic integrity might be disallowed, whereas in an older animal, such cells might slip past these quality-control mechanisms.