Gaming technology is a popular application for physical rehabilitation. However, the key problem with a considerable group of patients is that their muscle function is extensively compromised, which significantly narrows the population eligible for video game-based rehabilitation. We designed a training system to integrate gaming and functional electrical stimulation for the lower leg muscles. Such a system is expected to motivate individuals to exercise more, to assist muscle control, and to promote muscle strengthening. In our previous study, we demonstrated that the training improved the lower leg muscles’ strength and increased the range of motion of the ankle joints. Here we discuss some issues associated with a video game-based approach in rehabilitation, which need to be addressed. In particular, one of the biggest challenges is in maintaining a proper balance between flexibility of the game application to allow adaptation to the patient’s needs from physiological and functional perspectives, and attractiveness of the game interface, all while assuring the most efficient and motivating rehabilitation. As the next step, we decided to design different types of game-based exercises and to expand the variety of game strategies in order to promote and maintain activity of peripheral and central structures of the neuromuscular system, and to avoid the monotony of repetitive tasks. Our ultimate goal is to transfer re-training of movement skills practiced during video game-based interventions to the ability to complete real world tasks and participate in functional activities outside of therapy.