For context, we note that absolute errors in C-PCM solvation energies average 1.6 kcal/mol for small, chargeneutral solutes in water, if one compares calculated value of ∆G elst to the experimental free energies of solvation (∆G • ), with no corrections for nonelectrostatic interactions. (The experimental data have estimated uncertainties of only ±0.2 kcal/mol. 121,122 ) As such, discrepancies of 1-2 kcal/mol between HetPCM and Voronoi-PEqS are the same order of magnitude as the intrinsic accuracy of continuum solvation models themselves. For ions, the accuracy of C-PCM drops to 7-8 kcal/mol for aqueous solvation, although the uncertainties associated with the experimental data are ±3 kcal/mol for ions. In our judgement, HetPCM behaves reasonably well as assessed by comparison to the Voronoi-PEqS method and in comparison to the inherent accuracy of continuum solvation models, provided that ε nonp ≥ 4. The explanation for this is likely the rapidity with which the continuum solvation energy converges to the ε → ∞ limit, which is at least part of the reason why values ε > 4 have so little effect in enzyme modeling. In contrast, the combination of ε nonp = 1 with ε solv = 78.4 affords much larger discrepancies between HetPCM and Poisson electrostatic solvation energies.