In view of the excellent biocompatibility as well as the low cost, nanoscale ZnO shows great potential for drug delivery application. Moreover, The charming character enable nanoscale ZnO some excellent features (e.g. dissolution in acid, ultrasonic permeability, microwave absorbing, hydrophobic/hydrophilic transition). All of that make nanoscale ZnO reasonable choices for smart drug delivery. In the recent decade, more and more studies have focused on controlling the drug release behavior via smart drug delivery systems based on nanoscale ZnO responsive to some certain stimuli. Herein, we review the recent exciting progress on the pH-responsive, ultrasound-responsive, microwave-responsive and UV-responsive nanoscale ZnO-based drug delivery systems. A brief introduction of the drug controlled release behavior and its effect of the drug delivery systems is presented. The biocompatibility of nanoscale ZnO is also discussed. Moreover, its development prospect is looked forward.