Causal methods to interrogate brain function have been employed since the advent of modern neuroscience in the nineteenth century. Initially, randomly placed electrodes and stimulation of parts of the living brain were used to localize specific functions to these areas. Recent technical developments have rejuvenated this approach by providing more precise tools to dissect the neural circuits underlying behaviour, perception and cognition. Carefully controlled behavioural experiments have been combined with electrical devices, targeted genetically encoded tools and neurochemical approaches to manipulate information processing in the brain. The ability to control brain activity in these ways not only deepens our understanding of brain function but also provides new avenues for clinical intervention, particularly in conditions where brain processing has gone awry.