No currently available chemotherapy seems likely to substantially improve outcome in most patients with brain tumours. Several resistance-associated cellular factors, which were discovered in other cancer models, have also been identified in brain tumours. Although these mechanisms play some part in resistance in brain tumours, they are not sufficient to explain the poor clinical response to chemotherapy. There could be other brain-tumour-specific genetic profiles that are associated with tumour sensitivity to chemotherapy. There is increasing awareness that drug resistance in brain tumours is not a result of changes in single molecular pathways but is likely to involve a complex network of regulatory dynamics. Further insights into chemoresistance in brain tumours could come with comprehensive characterisation of their gene expression, as well as the genetic changes occurring in response to chemotherapy. Recent progress in high-throughput bioanalytical methods for genome-wide studies has made possible a novel research model of initial hypothesis generation followed by functional testing of the generated hypothesis.