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Body sensor networks (BSNs) are emerging cyber-physical systems that promise to improve quality of life through improved healthcare, augmented sensing and actuation for the disabled, independent living for the elderly, and reduced healthcare costs. However, the physical nature of BSNs introduces new challenges. The human body is a highly dynamic physical environment that creates constantly changing demands on sensing, actuation, and quality of service (QoS). Movement between indoor and outdoor environments and physical movements constantly change the wireless channel characteristics. These dynamic application contexts can also have a dramatic impact on data and resource prioritization. Thus, BSNs must simultaneously deal with rapid changes to both top-down application requirements and bottom-up resource availability. This is made all the more challenging by the wearable nature of BSN devices, which necessitates a vanishingly small size and, therefore, extremely limited hardware resources and power budget. Current research is being performed to develop new principles and techniques for adaptive operation in highly dynamic physical environments, using miniaturized, energy-constrained devices. This paper describes a holistic cross-layer approach that addresses all aspects of the system, from low-level hardware design to higher level communication and data fusion algorithms, to top-level applications.