Breakthroughs in assistive exoskeletons have occurred in the recent decade; both active and passive devices that provide partial joint moments in the lower limbs have reduced metabolic costs during walking by assisting muscle action. Musculoskeletal simulation is highly useful in describing the interaction between assistive moments, muscle-tendon mechanics, and walking energetics. In this study, we computed optimal assistive moments in ankle plantarflexion and hip flexion that produce minimal muscle activations during walking, described the muscle energetics, and estimated the potential reduction in metabolic cost. We described with analyses of muscle-tendon mechanics and motor control how reductions in muscle activation do not always result in metabolic cost savings.