Many crucial biological processes operate with surprisingly small numbers of molecules, and there is renewed interest in analyzing the impact of noise associated with these small numbers. Twenty-five years ago, Berg and Purcell showed that bacterial chemotaxis, where a single-celled organism must respond to small changes in concentration of chemicals outside the cell, is limited directly by molecule counting noise and that aspects of the bacteria's behavioral and computational strategies must be chosen to minimize the effects of this noise. Here, we revisit and generalize their arguments to estimate the physical limits to signaling processes within the cell and argue that recent experiments are consistent with performance approaching these limits.
