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Abstract
This Focus Issue of Science’s STKE complements the Science Special Issue on Single Molecules by highlighting technical advances that allow signaling events to be analyzed at the level of individual molecules within a single cell. Moving away from studies of populations of cells provides a number of benefits, including the reduction of biological "noise" and the easier detection of low-frequency events. Increasing the resolution with which cellular signaling is monitored will provide structural and mechanistic information of a more subtle and individual nature than was previously feasible, thereby providing better understanding of cellular variation, of molecular dynamics, and of how molecular structure influences function.