The article concerns potential harmful effects of exposure to lead. Although the occurrence of severe lead poisoning has receded in several countries, occupational exposure resulting in moderate and clinically symptomatic toxicity is still common. An earlier and precise characterization of an individual response is obligatory in order to assess the possible risks for human health. Biomarkers may fill important gaps in the path from exposure to a disease. Specifically speaking, emerging (DNA double strand breaks and telomeric DNA erosion) and validated (micronuclei induction and chromosomal aberrations) biomarkers of genotoxicity seem to provide evidence for the assessment of molecular and cellular damage. Moreover, identification of genetic variability with a key role in modulating genotoxic damage may help minimize risks for susceptible subjects. Further investigations are naturally needed to properly define their diagnostic and/or prognostic value as “early warning” signs of a long-term risk for a subsequent clinically overt disease.