This paper advocates disturbance observer-based control (DOBC) for uncertain nonlinear systems. Within this framework, a nonlinear controller is designed based on the nominal model in the absence of disturbance and uncertainty where the main design specifications are to stabilize the system and achieve good tracking performance. Then, a nonlinear disturbance observer is designed to not only estimate external disturbance but also system uncertainty/unmodeled dynamics. With described uncertainty, rigorous stability analysis of the closed-loop system under the composite controller is established in this paper. Finally, the robust control problems of a missile roll stabilization and a mass spring system are addressed to illustrative the distinct features of the nonlinear DOBC approach.