<p>This review summarizes research designed to enhance thermodynamic rigour in the quantitative characterization of protein self-association by direct analysis of sedimentation equilibrium distributions. The effects of thermodynamic nonideality have been incorporated into analytical approaches that not only afford experimental delineation of the monomer thermodynamic activity throughout a sedimentation equilibrium distribution but also take into account the composition dependence of species activity coefficients that arises from their consideration on the statistical-mechanical basis of excluded volume. Allowance for thermodynamic nonideality in terms of nearest-neighbor interactions should suffice for that iterative procedure. Attempts to eliminate the need for iterative analysis by expressing total protein concentration as a virial expansion in monomer activity have met with only limited success. The relevance of these scientific developments to their incorporation into the currently used numerical simulation approaches for the characterization of protein self-association by sedimentation equilibrium is also discussed.</p>