Since the 1950s, antifungal drug discovery has identified three classes of natural products (griseofulvin, polyenes and echinocandins) and four classes of synthetic chemicals (allylamines, azoles, flucytosine and phenylmorpholines) with clinical value against fungal infections. For life threatening fungal disease, the polyene amphotericin B is still a common choice despite toxic side-effects. The azoles remain the most widely used group of anti fungals active against a wide range of mycoses, benefiting from creative chemistry to boost their effectiveness. More recently, the echinocandins show great promise, with caspofungin licensed for clinical use in 2002 and two other molecules close to registration. New advances in molecular genetics afford the promise of revealing new antifungal targets, together with new agents to inhibit those targets specifically.