This work considers the problem of designing an active fault-isolation scheme for nonlinear process systems subject to uncertainty. The faults under consideration include bounded actuator faults and process disturbances. The key idea of the proposed method is to exploit the nonlinear way that faults affect the process evolution through supervisory feedback control. To this end, a dedicated fault-isolation residual and its time-varying threshold are generated for each fault by treating other faults as disturbances. A fault is isolated when the corresponding residual breaches its threshold. These residuals, however, may not be sensitive to faults in the operating region under nominal operation. To make these residuals sensitive to faults, a switching rule is designed to drive the process states, upon detection of a fault, to move toward an operating point that, for any given fault, results in the reduction of the effect of other faults on the evolution of the same process state. This idea is then generalized to sequentially operate the process at multiple operating points that facilitate isolation of different faults for the case where the residuals are not simultaneously sensitive to faults at a single operating point. The effectiveness of the proposed active fault-isolation scheme is illustrated using a chemical reactor example and demonstrated through application to a solution copolymerization of methyl methacrylate and vinyl acetate. (c) 2013 American Institute of Chemical Engineers AIChE J, 59: 2435-2453, 2013