In general, cells genetically engineered for stable and defined expression of xenobiotic-metabolizing enzymes are useful tools whenever a metabolism-related problem in toxicology and pharmacology is to be solved. It is the genetic and phenotypic nature of a given cell that determines its applicability. Mammalian cells have useful characteristics not given in bacterial, yeast or insect cells, which also may express xenobiotic-metabolizing enzymes. It is the problem to be solved and the question to be answered which determine the optimal choice for the best-suited expression system. There may even be subtle differences between mammalian cells of different species and organ origin, which might play a role in choosing a mammalian expression system. Thus, the level and specificity of the xenobiotic-metabolizing enzyme, the experimental testing conditions, and the biological endpoints present in a chosen cell are the most important criteria to be observed in the application of the mammalian expression systems.