Obesity and insulin resistance show increasing incidence in all ages, especially but not only, in western countries. The world epidemic on obesity imposes a higher prevalence of subjects with insulin resistance. This latter condition is associated with impairments on macro and microvascular function of different degrees. The exact interrelationship and meaning of this association and subsequent result on glucose homeostasis, vascular damage and end-organ impairments deserve further investigations. Techniques used to study the microcirculation could help researchers to clarify these questions. This chapter will focus on techniques employed in humans to investigate the microcirculation, endothelial reactivity, their significance and importance for the understanding of microcirculatory function with special focus on those employed and experienced by the authors.