Due to the excellent biocompatibility as well as the low cost, nanoscale ZnO shows a great potential in drug delivery application. The richness of the structures, easy modification and pleasant properties of nanoscale ZnO make these materials reasonable choices for drug delivery. In the recent decade, various ZnO nanostructures as well as nanohybrids have been carried out for optimizational drug loading and carrying. To control the drug release behavior, many nanoscale ZnO-based smart drug delivery systems which are responsive to particular stimuli via characteristics of ZnO (e.g. dissolution in acid, microwave absorbing, hydrophobic/hydrophilic transition) have been successfully synthesized. Herein, we review the recent exciting progress on the nanoscale ZnO-based drug delivery systems: from the passive to smart strategies.