Protein Arrays: Methods and Protocols is an introduction to protein array technology and its application to the multiplexed detection of proteins. Although protein array technology has some roots in gene array technology, it can only be described as a distant relative. Unlike DNA, with its established rules of base pairing, and therefore predictable biochemical behavior, proteins are rich with diversity. Proteins can be large or small, compact or extended, basic or acidic, hydrophobic or hydrophilic, and so on. Just as importantly, their behavior is determined by the environment in which they reside, and so the composition of the buffer in which experiments are performed has a dramatic impact on the outcome of the experiment. Thus, if the goal is to simultaneously measure the expression of a large number of proteins, these variables must be addressed. Not to be deterred, scientists have created a variety of solutions to successfully detect and ch- acterize multiple proteins simultaneously. It is the intent of this volume to introduce to the reader a set of technological solutions to the diversity problem as well as to provide the reader with some examples of practical applications of these technologies.