The microcirculation, integratively speaking, is distensible and contains 40%-50% of the total blood volume. Other than the mission of mass transport, the microcirculation and its endothelial cells have the role of regulation, signal transduction, proliferation, and repair. In this article, the emphasis is on the integrative role of the microcirculation on circulatory control and its therapeutic role on blood volume compensation. To introduce this topic, I first summarize the morphometry data on the blood volume distribution in the coronary, pulmonary, and mesentery circulation and then review the methodology developed in my laboratory to assess the microvascular volume change or shift of blood volume from microcirculation to macrocirculation. Evidence obtained through these studies indicates that the microcirculation can play a more important role as a reservoir to compensate for blood volume loss than the venous system. Reanalysis of published data also indicates that microvascular pooling, not hypovolemia, is the likely factor causing endotoxin shock or hypotension for hemodialysis patients. Understanding of the role of the microcirculation could lead to more effective diagnosis of cardiovascular deficiency and therapy for hypotension or low cardiac output with intervention through the microcirculation.