State estimation from plant measurements plays an important role in advanced monitoring and control technologies, especially for chemical processes with nonlinear dynamics and significant levels of process and sensor noise. Several types of state estimators have been shown to provide high-quality estimates that are robust to significant process disturbances and model errors. These estimators require a dynamic model of the process, including the statistics of the stochastic disturbances affecting the states and measurements. The goal of this article is to introduce a design method for nonlinear state estimation including the following steps: (i) nonlinear process model selection, (ii) stochastic disturbance model selection, (iii) covariance identification from operating data, and (iv) estimator selection and implementation. Results on the implementation of this design method in nonlinear examples (CSTR and large dimensional polymerization process) show that the linear time-varying autocovariance least-squares technique accurately estimates the noise covariances for the examples analyzed, providing a good set of such covariances for the state estimators implemented. On the estimation implementation, a case study of a chemical reactor demonstrates the better capabilities of MHE when compared with the extended Kalman filter. (C) 2010 American Institute of Chemical Engineers AIChE J, 57: 996-1007, 2011