This chapter presents the design and testing of a model-reference adaptive control (MRAC) scheme to compensate for the hysteresis effect of a class of piezo-actuated systems, which possess a second-order nominal model. Specifically, by treating the uncertainties as a lumped perturbation to the nominal system model, a scheme of MRAC with perturbation estimation (MRACPE) is developed and validated on a micropositioning system. As compared with existing works, the reported scheme allows the predesign of the maximum tracking error. It is capable of estimating the unmodeled perturbation of the system online.