In this paper, we present a cable-driven exoskeleton with variable stiffness for upper limb rehabilitation. Adjustable stiffness of the cable-driven exoskeleton is achieved by attaching a novel variable stiffness module (VSM) to each driving cable. The module is able to vary stiffness in a large range through changing cable tension. In this paper, a stiffness model is developed for a cable-driven exoskeleton to reveal the stiffness performance of the exoskeleton with the influence of VSMs. Based on the stiffness model, a controller with stiffness-oriented strategy is proposed to vary the stiffness of the exoskeleton. Experiments on a prototype of a cable-driven exoskeleton are conducted to validate the controller.