A workshop on innate immunity that took place this past autumn in Fira, Santorini, as part of the Aegean Conferences, provided tantalizing evidence about the early origin and evolutionary conservation of humoral and cellular components of innate immunity from sponges, flies and sea squirts to man, uncovered mechanistic aspects of its fundamental role in defense against disease, as well as the serious consequences of misdirected responses, and revealed the untapped potential of novel therapeutic approaches.