Developing hydrogel membranes and coatings of appropriate permeability characteristics is key to the success of a number bioartificial organ technologies. Key principles relevant to the design and application of hydrogels for such applications were reviewed. The first key point is that permeability is a function of both transport and thermodynamic properties, the diffusion coefficient and partition coefficient, respectively, and that these parameters can be evaluated separately. Although the aspect of partitioning often emphasized is size exclusion, this review points out that many other relevant interactions come into play, especially hydrophobic and electrostatic interactions, and that these phenomena can dominate size exclusion. Similarly, while the diffusion coefficient also is strongly dependent upon size, other interactions can also cause diffusivity to deviate from theories which consider only solute size and gel swelling. For example, the heterogeneity of hydrogel networks can result in permeabilities that fail to decline as much as might be anticipated if networks were uniform.