Antibacterial discovery research has been driven, medically, commercially and intellectually, by the need for new therapeutics that are not subject to the resistance mechanisms that have evolved to combat previous generations of antibacterial agents. This need has often been equated with the identification and exploitation of novel targets. But efforts towards discovery and development of inhibitors of novel targets have proved frustrating. It might be that the 'good old targets' are qualitatively different from the crop of all possible novel targets. What has been learned from existing targets that can be applied to the quest for new antibacterials?