Solute diffusion in hydrogels is important in many biotechnology fields. Solute behavior in hydrogels has been explained in terms of reduction in hydrogel free volume, enhanced hydrodynamic drag on the solute, increased path length due to obstruction, and a combination of hydrodynamic drag and obstruction effects. In this article the various mathematical models derived to explain and predict solute diffusion in hydrogels are reviewed and tested against literature data. These models can be divided into those applicable to hydrogels composed of flexible polymer chains (i.e., homogeneous hydrogels) and those composed of rigid polymer chains (i.e., heterogeneous hydrogels). For homogeneous hydrogels it was determined that a scaling hydrodynamic model provided the best explanation for solute diffusion, while for heterogeneous hydrogels obstruction models were more consistent with the experimental data. Both the scaling hydrodynamic model and the most appropriate obstruction model contain undefined parameters which must be clarified in order for these models to gain widespread acceptance.