The use of combination chemotherapy to cure acute lymphoblastic leukaemia (ALL) in children emerged in the 1980s as a paradigm for curing any disseminated cancer, and many of the therapeutic principles were subsequently applied to the treatment of other disseminated human cancers. Similarly, elucidation of the pharmacogenomics of ALL and its translation into new chemotherapeutic approaches might serve as a model for optimizing the treatment of other human cancers. Germline polymorphisms and gene-expression patterns in ALL cells have been linked to the toxicity and efficacy of chemotherapy for ALL and are beginning to emerge as useful clinical diagnostics.