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Understanding and repairing complex biological systems, such as the brain, requires technologies for systematically observing and controlling these systems. We are discovering new molecular principles that enable such technologies. For example, we discovered that one can physically magnify biological specimens by synthesizing dense networks of swellable polymer throughout them, and then chemically processing the specimens to isotropically swell them. This method, which we call expansion microscopy, enables ordinary microscopes to do nanoimaging – important for mapping molecules throughout cells, and cells throughout brain circuits. Expansion of biomolecules away from each other also decrowds them, enabling previously invisible nanostructures to be labeled, and seen. As a second example, we discovered that microbial opsins, genetically expressed in neurons, could enable their electrical activities to be precisely controlled in response to light. These molecules, called optogenetic tools, enable causal assessment of how neurons contribute to behaviors and pathological states, and are yielding insights into new treatment strategies for brain diseases. They are also beginning to be used in human patients, in experimental clinical contexts like treating blindness. Finally, we are developing, using new strategies such as robotic directed evolution, fluorescent reporters that enable the precision measurement of signals such as voltage. In order to reveal relationships between different molecular signals within a cell, we are developing spatial and temporal multiplexing strategies that enable many such signals to be imaged at once in the same living cell, using ordinary microscopes, and requiring only fully genetically encoded constructs. We share all these tools freely, and aim to integrate the use of these tools so as to enable comprehensive understandings of neural circuits.