Although general anaesthesia has been of tremendous importance for the development of surgery, the underlying mechanisms by which this state is achieved are only just beginning to be understood in detail. In this review, we describe the neuronal systems that are thought to be involved in mediating clinically relevant actions of general anaesthetics, and we go on to discuss how the function of individual drug targets, in particular GABA(A)-receptor subtypes, can be revealed by genetic studies in vivo.