Gut flora and gut contents can be considered as a system with huge metabolic capacity, qualitatively and quantitatively different from the body cells and organs. That system changes along with life and nutrition, but despite broad investigation has not yet been defined satisfactorily. In many cases inter individual and intra individual differences in drug metabolism could be linked to variations in the gut flora metabolism. Gut flora metabolism of drugs and other xenobiotic metabolites excreted in bile is the key phase responsible for enterohepatic circulation. In the last decade there has been more and more evidence for the crucial role of the gut flora cysteine conjugate beta-lyase in the metabolism of cysteine conjugates. A new pathway for paracetamol cysteine conjugate metabolism has been directly linked with gut flora activity, as demonstrated in our studies. Nowadays, it is quite clear that gut flora metabolism must be considered an integral part of drug metabolism and toxicity studies.