Being able to observe cellular signalling events in action is the life scientist's dream, but the technical challenge for microscopy is daunting. The inside of the cell has been likened to a thick soup in which individual signalling events are obscured by background ‘noise’. There are two problems to overcome. The first problem is spatial, and involves locating the molecules and structures of interest. The second is temporal: following molecules over time to see when, and how quickly, they move to their targets. This article examines important advances in optical microscopy that not only make live-cell imaging a reality, but that even allow researchers to track individual molecules, in real time, with nanometre resolution.

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