Besides being important occupational hazards, lead and cadmium are nowadays metals of great environmental concern. Both metals, without any physiological functions, can induce serious adverse health effects in various organs and tissues. Although Pb and Cd are non-redox metals, one of the important mechanisms underlying their toxicity is oxidative stress induction as a result of the generation of reactive species and/or depletion of the antioxidant defense system. Considering that the co-exposure to both metals is a much more realistic scenario, the effects of these metals on oxidative status when simultaneously present in the organism have become one of the contemporary issues in toxicology. This paper reviews short and long term studies conducted on Pb or Cd-induced oxidative stress in blood, liver and kidneys as the most prominent target organs of the toxicity of these metals and proposes the possible molecular mechanisms of the observed effects. The review is also focused on the results obtained for the effects of the combined treatment with Pb and Cd on oxidative status in target organs and on the mechanisms of their possible interactions.