This dissertation presents numerical and experimental results on the effects of Personal Cooling Devices (PCDs) on the energy consumption of buildings and the thermal comfort of occupants. The objective of this analysis was to quantify the tradeoffs of thermal comfort and energy savings associated with PCD technology. Furthermore, this investigation included an electrical cost analysis associated with PCDs at the building level for different cities across the United States. The results of energy and cost analyses, at the building level, indicated the potential for cooling energy and cost savings associated with shifting the electricity consumption during the peak hours to the off-peak hours of the day. The numerical analysis of human thermal comfort demonstrated the potential for PCDs to regulate human thermal comfort at warm environmental conditions. The thermal comfort level achieved in the numerical simulations were within the limits recommended by ASHRAE Standard 55. In addition, the numerical simulations permitted the evaluation of PCD performance based on thermal comfort, and the amount of sensible heat remove from the human body. The experimental work evaluated the performance of PCDs using both subjective and objective measurements of thermal comfort for 14 human subjects. The results demonstrated the ability of a PCD to change and maintain acceptable thermal comfort micro-environments for human subjects under warm conditions. Furthermore, the results showed that a PCD had measurable effects on physiological variables that control the thermoregulatory process of the human body. Specifically, variables such as skin temperature and heart rate variability in the time and frequency domain responded to the micro-environment created by the PCD. This research established a relationship between skin temperature, heart rate variability, and thermal comfort. Overall, this investigation performed a comprehensive analysis of the interaction of PCDs with: building energy consumption, human subjects, and human physiological processes; and demonstrated the potential to recognize human subjects’ thermal comfort based on physiological signals.