Nearly a third of proteins encoded in the human proteome contain intrinsically disordered regions, which lack a discernible structure-function relationship. Yet, these proteins can adopt transient conformations in order to carry out a wide-variety of functions, challenging the classical structure-function paradigm. In this talk I will discuss past and present efforts to utilize peptide aptamers to modulate the disordered proteome in the context of physiology and human disease. These studies reconcile simulated protein ensembles, which populate vast free energy landscapes, to macroscopic solution biophysical observations. Discerning subtle differences between physiological and pathological protein behaviors is essential for understanding and exploiting the biophysics of amyloid diseases, and can inform the construction of disordered biomaterials through synergistic integration of state-of-the-art theoretical and experimental techniques.