Zearalenone is a lactone derivative of the resorcylic acid produced by various Fusarium species that are widely found in foods and animal feeds. Zearalenone exerts species-specific estrogenic effects, possibly because of the metabolism differences arising from reduction, hydroxylation, or glucuro-conjugation. Contamination can occur in the field through infringement of the plant or takes place during crop storage. Zearalenone is resistant to most common treatments that occur during food manufacturing and interacts with both types of estrogen receptors and substrates of several hepatic enzymes. The results of these diverse interactions are manifested by functional and morphological alterations of the reproductive organs. The main objectives of the present research were to elucidate the effects of contaminated aliments with zearalenone on the detoxification proteins. Complementary approaches have been used: development of analytical tools for pharmacokinetics studies; determination of zearalenone in vivo effects on the detoxification enzymes expression and transformation within animal organism; and assessment of zearalenone in vitro molecular mechanisms.