Vacuum membrane distillation is a membrane-based separation process considered here to remove volatile organic compounds from aqueous streams. Microporous hydrophobic membranes are used to separate the aqueous stream from a gas phase kept under vacuum. The evaporation of the liquid stream takes place on one side of the membrane, and mass transfer occurs through the vapor phase inside the membrane. The role of operative conditions on the process performance is widely investigated in the case of dilute binary aqueous mixtures containing acetone, ethanol, isopropanol, ethylacetate, methylacetate, or methylterbutyl ether. Temperature, composition, flow rate of the liquid feed, and pressure downstream the membrane are the main operative variables. Among these, the vacuum-side pressure is the major design factor since it greatly affects the separation efficiency. A mathematical model description of the process is developed, and the results are compared with the experiments. The model is finally used to predict the best operative conditions in which the process can work for the case of benzene removal from waste waters.