The primary purpose of perioperative IV fluid administration is to preserve tissue perfusion by maintaining or restoring the effective circulating intravascular volume. Fluids are drugs that produce beneficial or harmful effects dependent upon their composition, osmotic potential, kinetics, and dose. Appropriate dosing requires an understanding of body fluid compartments, fluid balance, and the administered fluids' behavior in the body. Anesthetic drugs and general anesthesia produce CNS, neuroendocrine, and macro-/microvascular hemodynamic effects. These effects modulate the response to IV fluid administration and promote interstitial fluid accumulation, third-space fluid loss, and fluid overload. This narrative review discusses current knowledge regarding anesthesia-associated physiologic and IV fluid kinetic changes that influence the efficacy of IV fluid administration during the intraoperative period. A rationale for intraoperative fluid dosing that addresses intraoperative hypotension, blood loss, and practices that promote fluid overload is provided. Intraoperative IV fluid administration should be individualized and monitored by dynamic goal-directed methods that evaluate fluid responsiveness.