Recent work on the thermodynamics of protein denatured states is providing insight into the stability of residual structure and the conformational constraints that affect the disordered states of proteins. Current data from native state hydrogen exchange and the pH dependence of protein stability indicate that residual structure can modulate the stability of the denatured state by up to 4 kcal mol-1. NMR structural data have emphasized the role of hydrophobic clusters in stabilizing denatured state residual structures, however recent results indicate that electrostatic interactions, both favorable and unfavorable, are also important modulators of the stability of the denatured state. Thermodynamics methods that take advantage of histidine-heme ligation chemistry have also been developed to probe the conformational constraints that act on denatured states. These methods have provided insights into the role of excluded volume, chain stiffness, and loop persistence in modulating the conformational preferences of highly disordered proteins. New insights into protein folding and novel methods to manipulate protein stability are emerging from this work.