Published clinical observations underline the difficulty of defining with epidemiological studies the effects that chemicals such as drugs, illicit substances environmental and workplace pollutants might have on the offspring through the male parent. The Authors highlight how defining this issue might help both guide preclinical research and evaluate correctly clinical observations which are often difficult to interpret based only on observations in the female parent. Clinical research already available shows that some chemicals are able to modify fertility by acting either at the neuroendocrine level or on the testis. However, it is more difficult to identify and quantify the potential damage to the offsprings during the different phases of pregnancy and postnatal life. Finally, the Authors discuss the parameters that should be considered to obtain an algorithm for evaluating the reproductive risk in males, along the lines of the risk for the embryo and fetus due to the use of drugs during pregnancy. Moreover, it is suggested that among the unwanted effects of drugs and pollutants, those related to the different components and phases of the male reproductive function be reported also in relation to the patient's age.