Chemotherapy lacks efficacy in most histological types of primary human brain tumours and has, for most types, failed to improve outcome for patients. The unsatisfactory results with chemotherapeutic intervention in these cancers have been chiefly attributed to tumour-cell resistance. This review summarises some of the major molecular markers that, although neither exclusive for nor specific to brain tumours, have been associated with the formation of a chemoresistant phenotype. Elucidation of the cellular mechanisms involved in resistance regulation is needed for future progress in efficient approaches to selective modulation of drug resistance in these lesions.