In this review we present the principles behind protein overexpression in bacteria, emphasizing how this biosynthetic system can be manipulated to generate large quantities of proteins for study. In addition to the classical (molecular biological) methods for constructing protein-overproducing bacterial, we discuss our recently developed (chemical/enzymatic) method, the Expression-Cassette Polymerase Chain Reaction (ECPCR). The chemical/enzymatic transformation of an unexpressable to an expressable gene afforded by ECPCR can routinely be carried out in the experimental organic chemistry laboratory, hence, ECPCR offers a convenient point of entry for chemists interested in macromolecular science.