The physicochemical concepts that underlie our present ideas on the structure and assembly of the "macromolecular machines of gene expression" are developed, starting with the structure and folding of the individual protein and DNA components, the thermodynamics and kinetics of their conformational rearrangements during complex assembly, and the molecular basis of the sequence specificity and recognition interactions of the final assemblies that include the DNA genome. The role of diffusion in reduced dimensions in the kinetics of the assembly of macromolecular machines from their components is also considered, and diffusion-driven reactions are compared with those fueled by ATP binding and hydrolysis, as well as by the specific covalent chemical modifications involved in rearranging chromatin and modifying signal transduction networks in higher organisms.