A focused review of the physiologic mechanisms of colloid and crystalloid fluid resuscitations for acute critical illness is presented. This review suggests that postresuscitation plasma volume, cardiac output, left ventricular mechanical performance, and global and microcirculatory O2 supplies are more favorable with colloid therapy. Conversely, crystalloid may adversely affect microcirculatory blood flow and resultant O2 supply and use by ischemic tissues in shock. Poor relief of global and regional hypoxia may persist in critically ill patients after resuscitation with crystalloid.