The objective of this article is to review the spectrum of mathematical models that have been developed to describe drug release from hydroxypropyl methylcellulose (HPMC)-based pharmaceutical devices. The major advantages of these models are: (i) the elucidation of the underlying mass transport mechanisms; and (ii) the possibility to predict the effect of the device design parameters (e.g., shape, size and composition of HPMC-based matrix tablets) on the resulting drug release rate, thus facilitating the development of new pharmaceutical products. Simple empirical or semi-empirical models such as the classical Higuchi equation and the so-called power law, as well as more complex mechanistic theories that consider diffusion, swelling and dissolution processes simultaneously are presented, and their advantages and limitations are discussed. Various examples of practical applications to experimental drug release data are given. The choice of the appropriate mathematical model when developing new pharmaceutical products or elucidating drug release mechanisms strongly depends on the desired or required predictive ability and accuracy of the model. In many cases, the use of a simple empirical or semi-empirical model is fully sufficient. However, when reliable, detailed information are required, more complex, mechanistic theories must be applied. The present article is a comprehensive review of the current state of the art of mathematical modeling drug release from HPMC-based delivery systems and discusses the crucial points of the most important theories.