Physical sensors, defined by their direct chemical interaction with the sensing environment, are a valuable and often essential contribution to the solution of stringent chemical sensing problems. Methods for conditioning signals from these sensors to optimize their presentation to subsequent decision-making models in the signal processing flow are presented. The assembly of sensors into an array and the preprocessing of these signals are the two primary techniques for conditioning a chemical image for concentration detection, chemical discrimination, and, in some cases, odor localization. Array optimization involves locating the point at which adding additional sensors to an array generates more noise than information and is highly dependent on the application and number of analytes to be sensed or differentiated. Signal preprocessing techniques include noise reduction, feature extraction, the reduction of array inputs, and the scaling of individual sensor signals and provide a means by which to reconstruct an array of chemical sensor signals into a subset of information that enables a decisionmaking model to do its job with greater efficiency and accuracy. In this chapter, surveys of methods are accompanied by representative examples employing a wide variety of sensors including ChemFETs, chemiresistors, acoustic wave devices, and surface plasmon resonance sensors.