Prostaglandins are a group of biologically active compounds that play major roles in human physiology in both health and disease. They function in many different ways and in all major organs. This article reviews the basic physiology of prostaglandins and their application to specific effects on these systems in normal and abnormal clinical states. The critical therapeutic implications of the use of nonsteroidal antiinflammatory drugs in altering organ homeostasis are also examined. References were taken from Medline, Embase, and Index Medicus from 1966 to September 2005. A search was done with keywords, including prostaglandins, nonsteroidal antiinflammatory drugs, inflammation, arachidonic acid, Cox-1 (cyclooxygenase-1), and Cox-2 (cyclooxygenase-2). There was a close correlation and predictability between basic prostaglandin physiology and the anticipated effects of these compounds on the heart, lungs, kidneys, gastrointestinal tract, bones and joints, brain, and male and female reproductive systems. These effects are organ and tissue specific. Despite these findings, unexplained and sometimes paradoxical physiologic responses were identified. A prime example of this is the role of prostaglandins in bone metabolism demonstrating both stimulatory and inhibitory effects. In addition all NSAIDs have the potential to impair the normal physiologic effects of prostaglandins depending primarily on the specific organ and the clinical setting. Prostaglandins are regulatory compounds that play important roles in many physiologic processes in the human body. An understanding of the basic science of prostaglandins is valuable in anticipating the organ-specific biologic effects of these unique compounds in health and disease. However, at selected sites and under different physiologic conditions, unexplained and sometimes paradoxical effects are generated. Impairment of their regulatory functions can lead to significant short- or long-term organ dysfunction.