Efforts to discover new cancer drugs and predict their clinical activity are limited by the fact that laboratory models to test drug efficacy do not faithfully recapitulate this complex disease. One important model system for evaluating candidate anticancer agents is human tumour-derived cell lines. Although cultured cancer cells can exhibit distinct properties compared with their naturally growing counterparts, recent technologies that facilitate the parallel analysis of large panels of such lines, together with genomic technologies that define their genetic constitution, have revitalized efforts to use cancer cell lines to assess the clinical utility of new investigational cancer drugs and to discover predictive biomarkers.