Of the plethora of pyrimidines, pyrimidine nucleosides, analogues and prodrug derivatives that have been synthesised and evaluated as anticancer agents, only two are in general clinical use. The long-studied 5-fluorouracil (5-FUra (1), see Scheme 9.1), and some nucleoside and prodrug derivatives, are used regularly for the treatment of breast cancer, tumours of the gastrointestinal tract and other solid tumours. Acute leukaemias and lymphomas, especially acute myelogenous leukaemia, often respond successfully to l-(β-D-arabinofuranosyl)cytosine (araC (2)). The symmetrical triazine analogue of cytidine, 5-azacytidine (5-azaCyd (3)) and its 2’-deoxy, arabino and dihydro derivatives have been studied extensively, and 5-azaCyd is available as an investigational antitumour drug effective against leukaemias. This chapter presents outlines of basic synthetic methods which have been reported for the preparation of 5-FUra (1), araC (2), 5-azaCyd (3) and selected nucleoside and/or prodrug derivatives. Generally, only an initial type of synthetic approach is given. Subsequent work that employed the basic synthetic strategies is not usually quoted unless a significant conceptual contribution was made in addition to yield improvements and/or industrially useful modifications. Some discussion of molecular modes of anticancer action that involve defined chemical entities, certain metabolic conversions, and properties and interactions of prodrugs are presented.