One of the greatest challenges in neuroscience has been to monitor electrical activity and biochemistry in populations of identified neurons in vivo. Recent work on new microscopy techniques has moved the field considerably further in that direction. In particular the combination of modern imaging technology and genetic labeling methods heralds a bright future for neuronal circuit analysis. Biosensor development complements these efforts on the "indicator side" by providing probes for key events crucial for an understanding of neuronal function and plasticity. Moreover it aims at overcoming long-standing limitations in the ability to monitor neuronal activity and biochemistry in intact tissues and over longer periods of time.