This paper reviews biologic and epidemiologic evidence that prefertilization and perifertilization exposures to fathers influence a variety of reproductive outcomes, including fertilization, miscarriage, low birth weight, congenital anomalies, cancer, and neurodevelopmental and other childhood health problems. Males and females bring an equal number of chromosomes to their progeny, but their genomes may affect different aspects of reproduction. While the key male role principally ends at fertilization, there is growing experimental and human evidence that factors relating both to prefertilization and perifertilization exposure also play a role post fertilization. Some negative human epidemiologic findings reflect the fact that routinely gathered information usually generates detailed descriptions of maternal exposures and does not collect records regarding prefertilization paternal exposures. The absence of extensive human evidence should be interpreted as a deficiency in research rather than an absence of male-mediated adverse reproductive outcomes. More than 60 different compounds or industrial processes have been identified as increasing defects in human sperm and possibly increasing the risk to offspring from male-mediated exposures. Further research needs to include better characterizations of both maternal and paternal prefertilization and perifertilization exposures, in order to assess more accurately their relative effects. Pediatricians confronted with adverse pregnancy and antenatal health outcomes should obtain detailed information on relevant prefertilization exposures of both parents.