In human-robot interaction frameworks maximizing the team efficiency is crucial. However, it is also essential to mitigate the physical and cognitive workload experienced by the shop-floor worker during the collaborative task. In this chapter we first investigate the impact of the robot interaction role (whether being leader or follower during cooperation) on both the human physiological stress and production rate. Based on that, a game-theoretic approach is proposed to model the trade-off between the maximization of the human performance and the minimization of the human cognitive stress. Then, we describe a closed-loop robot control strategy that, based on the proposed game-theoretic model, enables the robot to simultaneously minimize the human cognitive stress and maximize his/her performance during cooperation, by adjusting its role. Eventually, a real-time task allocation strategy is proposed to both ensure the minimization of the human physical fatigue and the effectiveness of the production process. This method relies on a new sophisticated musculoskeletal model of the human upper-body. All these methodologies have been experimentally tested in realistic human-robot collaborative scenarios involving several volunteers and the ABB IRB 14000 dual-arm “YuMi" collaborative robot.