Cyber-Physical Systems which detect and use human psychological and physiological states as feedback to their control-loop are known as Human-in-the-Loop (HITL). The current understanding of the general requirements and theory behind this new class of systems is, however, still limited. This paper attempts to contribute towards their development by presenting a conceptual model that integrates some of the major ideas spread throughout the literature. In addition, it also discusses how the acquisition of a human’s state requires reliable networking. In this respect, an architecture for HITL management of networking configurations is presented. This architecture is implemented in an experimental scenario where a smartphone system attempts to positively impact mood by dynamically adapting privacy settings and networking interfaces to the user’s emotions. In this scenario, good hand-off performance is crucial for improving Quality of Experience and reliability. Several experiments regarding emotional classification and mobile handoff are also presented and discussed.