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Human-in-the-Loop Cyber-Physical-Systems (HiLCPS) is a challenging and very promising class of applications with immense potential of impacting daily lives of many people. HiLCPS systems measure cognitive activity through body and brain sensors, infer the intent through analysis on an embedded system, they then translate the intent into robot control signals influencing the physical environment by robotic actuators, where the effects are then again observed by the human as an input for new decisions -- closing the loop. This article overviews HiLCPS opportunities and design challenges from the view of 4 disciplines: embedded system design, brain-computer interface algorithm design, assistive robotics, and innovative networking. The article outlines a common design scheme unifying these disciplines.