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Functional electrical stimulation (FES) is the most commonly used technology for improving motor function in individuals who have spinal cord injury. Despite the wide range of FES applications reported in the literature, few electrical stimulation systems that can generate meaningful functional outcomes are currently available for use outside research laboratories. We tested proportional-integral-derivative, gain scheduling, and sliding mode control closed-loop control algorithms in a simulation of electrically induced knee extension against gravity to uncover some of the reasons why closed-loop control is not being more widely used in real-world FES systems. We also subjected the simulated FES system to muscle fatigue, muscle spasms, and the effects of muscle retraining. All of the controllers exhibited significantly degraded performance when these real-world nonlinear effects were included in the simulation. Moreover, all of the controllers were sensitive to variation in the parameters of the muscle recruitment function, which are subject to change during real-world FES use. We suggest several ways to improve the performance of closed-loop control algorithms for use in FES applications. We believe that closed-loop controllers have an important place in future FES applications, but the performance of these algorithms must be greatly improved before they can be implemented in real-world systems.