Dissolution-controlled drug delivery systems are characterized by a phase erosion of the polymer carrier that is associated with fast or slow dissolution of the macromolecular chains. The molecular nature of the dissolution phenomenon was examined by analyzing the water transport process and the subsequent polymer chain disentanglement that is usually characterized by a snake-like motion of the chain (reptation). The results indicate that the polymer molecular weight, water, polymer and drug diffusion coefficients, equilibrium water concentration in the polymer, and water-polymer interaction parameter can control the mechanism and rate of drug release. A new model for this process was developed, and its predictions are compared with experimental studies of drug delivery from poly (vinyl alcohol)-based systems.