Understanding how the diverse cells of the nervous system generate sensations, memories and behaviors is a profound challenge. This is because the activity of most neurons cannot easily be monitored or individually manipulated in vivo. As a result, it has been difficult to determine how different neurons contribute to nervous system function, even in simple organisms like Drosophila. Recent advances promise to change this situation by supplying molecular genetic tools for modulating neuronal activity that can be deployed in a spatially and temporally restricted fashion. In some cases, targeted groups of neurons can be 'switched off' and back 'on' at will in living, behaving animals.