The polarizable continuum model (PCM) is a popular approach for incorporating solvation into electronic structure calculations that describes electrostatic and polarization interactions between an atomistic solute and its continuum environment. Although accurate modeling of solvation energies requires that this model be augmented by non-electrostatic contributions, what the PCM does correctly is to furnish boundary conditions for an electronic structure calculation that are superior to gas-phase boundary conditions. For typical solutes that are amenable to quantum chemistry calculations, the PCM contributes only modest computational overhead. Linear-scaling PCM algorithms have been developed for much larger solutes, extending the use of PCM boundary conditions to cases where the atomistic region is described using a quantum mechanics/molecular mechanics (QM/MM) formalism. PCM calculations on full proteins have been reported. For large protein models, however, it is not always clear that an isotropic dielectric medium is the appropriate choice of boundary conditions.