Bacteria sense the chemical world using a variety of mechanisms that include the frequently described two-component system (TCS), which comprises a sensor kinase and response regulator, to regulate gene expression in response to environmental cues. One of the best and most widely studied versions of the TCS is the system that controls chemotaxis in Escherichia coli. The chemotaxis machinery includes components not found in other TCS to regulate motility and is therefore an exception to the rule for two-component signaling. The hallmark feature of the chemotaxis system is the presence of an adaptation module in which the sensor receptor protein is posttranslationally modified to attenuate ligand-induced signaling, a mechanism not yet identified for the more widely distributed prototypical TCS. More recently, variations on the chemotaxis system itself have been identified and they are termed chemosensory systems and are the subject of this review. Extensive research has provided a perspective on TCS signaling and indicates that variation and diversity for the standard two-component system are predominant in the microbial world.