This chapter examines the understanding of thermoregulatory responses influenced by exercise-related factors, focusing on human perspiration and cutaneous circulation. It discusses the influence of physiological and health conditions on these thermoregulatory responses. Moreover, as exercise continues, the cardiovascular and body fluid system intervene thermoregulatory responses to maintain these regulatory systems. The chapter summarizes the primary non-thermal modifiers of sweat rate and skin blood flow during exercise. Cardiovascular drift occurs after —10 min of moderate to high intensity exercise. Internal body temperature can be maintained in a narrow range if thermoregulatory heat dissipation is fully functional during exercise. Certain disease conditions as well as bodily injury can have a detrimental impact on thermoregulation. Diseases, including multiple sclerosis and diabetes mellitus, can alter neural pathways within the central nervous system and the peripheral nervous system, respectively, leading to impairments in sweating and skin blood flow.