At present, there is no simple predictive test to identify an active anticancer agent in man; the development of compounds that finally reach the clinic commonly reflects a mixture of intelligence and guesswork, dogged persistence and a major element of luck. The discovery of temozolomide is the result of all the above but, crucially, was built on a symbiotic relationship between the laboratory sciences of chemistry and pharmacology, and an inquisitive clinical culture keen to explore the efficacy of a new drug in the only animal that really matters-the patient suffering from cancer. The significant molecules which were stepping stones on the pathway to temozolomide are shown in Figure 1. Their common feature, spanning pyrazolo-1, 2, 4-triazines and aryldimethyltriazenes in the early 1960s to temozolomide of the mid 199Os, is the presence of arrays of nitrogen atoms