An overview of current heterologous expression systems for xenobiotic metabolising enzymes is given with a special emphasis on the yeast expression system. In a first part, basic properties and relative advantages and drawbacks of each expression system are considered. The second part is dedicated to humanized yeast strains allowing human P450 expression in a tailored redox environment and to the possibility to use such strains to simulate complex metabolisms involving a combination of phase I and phase II reactions. The last part presents how the association of numeric simulation to yeast expression can help in understanding rules controlling metabolic profiles in xenobiotic-acting multienzymatic systems.