This paper deals with the physical and mathematical modelling description of drug release from matrix systems. In the introduction, matrix systems are considered in the wide frame of the controlled release systems and the concept of mathematical model is briefly discussed. Then, matrix structure and topology are matched, analysing the characteristics of the three-dimensional network constituting them. In this context, drug release mechanisms are considered with particular emphasis on the key factors ruling the release kinetics, such as matrix swelling, erosion, drug dissolution (re-crystallisation), drug diffusion, drug - polymer interaction, initial drug distribution and particle size distribution (for powdered matrix systems). The mathematical modelling section firstly considers the empirical and semi-empirical models that have the great advantage of showing analytical solutions. Then, the attention is focused on theoretical approaches regarding matrix swelling equilibrium and kinetics, drug dissolution, drug diffusion, drug - polymer interaction, initial drug distribution and matrix erosion. Finally, release kinetics from polydispersed spherical particles is studied. This review points out the fact that the comprehension of the phenomena ruling drug release from matrix systems is appropriate from both the physical and modelling point of view, although further improvements are always possible and desirable.