The resistance of bacteria to beta-lactam antibiotics is usually associated with production of the enzyme, beta-lactamase, which inactivates the beta-lactam molecule. In the long search for inhibitors of bacterial beta-lactamase the first clinically useful agent, clavulanic acid, was isolated as a metabolite of Streptomyces clavuligerus. Robert Sutherland describes the background to the demonstration of clinical efficacy of combinations of clavulanic acid and other agents with penicillins which has confirmed beta-lactamase inhibitors as one solution to the problems posed by beta-lactamase-producing bacteria.