A critical review of mathematical modeling for simulation of environmentally sensitive hydrogels is presented for application of drug delivery. The review demonstrates that there have been large numbers of published studies on the model development, although the majority of investigations in the research area of the drug delivery are experimental-based. Therefore, a systematical review of mathematical modeling of environmentally sensitive hydrogels is necessarily provided through comprehensive assessment on several critical developments of mathematical models to simulate the hydrogels for mechanisms of drug release. The present review classifies the developed models into the fundamental and empirical/semi-empirical groups and also discusses the properties and performance of the hydrogels as drug delivery system in kinetics and equilibrium.