In vitro models have been intensively developed for several years for selecting new anticancer agents. The National Cancer Institute has even chosen as a primary screen of new molecules a panel of 60 human tumor cell lines. However, it may seem hazardous to rely too much on in vitro models for the discovery and selection of new anticancer drugs: (1 because no metabolism of the compounds occurs in cell culture; (2 because an in vitro cell line cannot be representative of an in situ tumor cell population; (3 because antiproliferative activity is only part of antitumor activity; (4 because the toxicologic properties of the molecules are not taken into account by in vitro systems; (5 because cell cultures do not allow any selectivity study between tumor cells and normal cells. With examples drawn from three different therapeutic classes, anthracyclines, taxoids and camptothecin derivatives, we show that in vitro tests are insufficiently predictive of antitumor potential. The excess of confidence allowed to these models may lead to premature decisions which are not after that justified by clinical trials.