In vitro assays are increasingly being used in drug metabolism studies to screen novel chemicals. Their advantages are twofold: first, they allow testing early in the drug discovery phase, providing important information on chemical characteristics; second, human cells or cell constituents can be utilized, increasing the relevance to man. However, the process of isolation, transformation or storage of these cell systems may alter their phenotype (and, in the case of tumour-derived cell lines, genotype as well). A review of the systems currently employed shows that, whereas all systems have their own caveats, it is possible to find an appropriate system for any particular question that is asked.