Abstract: Ctesias (fifth century BC) recounted contemporary Persian beliefs of white Indian animals which had a white horn, black in the centre and flaming red at the pointed tip, projecting from their forehead. Reinforced by classical and medieval writers, travellers, biblical warrant and trade in narwhal tusk, the unicorn became firmly established in European mythology. Increasing popularity as an alexipharmic, prophylactic and counter-poison through the fifteenth to seventeenth centuries led to rising demand and rapidly inflating prices. Debate raged as to which was the ‘true unicorn’ ( Unicornum Verum ), narwhal tusks or mammoth ivory ( Unicornu Fossile ); shavings and powders of both were incorporated into a bewildering array of medicinal mixtures while fraudulent alternatives flooding the markets required the employment of discriminatory tests. Further alternatives with supposedly similar properties included the (probably smectite) clays of Terra Sigillata Strigoniensis or Terra Silesiaca ( Unicornu Minerale ), and an alchemical preparation ( Unicornu Solare ). The supposed therapeutic application and wide range of delivery systems of all types of unicorn horn medicines are reviewed in detail for the first time. Particularly popular as an antidote in plague medicines, the use of alicorn (unicorn horn) simples declined to extinction with the increasingly empirical approach to pharmacy of the mid-eighteenth century.