The absorption, distribution, and retention of vitamin C are primarily governed by the family of sodium-dependent vitamin C transporters (SVCTs). The diverse expression and concentration dependency of these transporters throughout the body have resulted in the highly complex, compartmentalized, and nonlinear pharmacokinetics of vitamin C at physiologic levels. Moreover, studies of human SVCTs have identified a number of polymorphisms and suggested that these may have significant impact on the pharmacokinetics of vitamin C. In addition to its many biological functions, the putative effect of vitamin C in cancer treatment has been the subject of much debate. However, following the critical realization that oral administration of vitamin C profoundly limits the maximum achievable plasma concentration, vitamin C is currently being reinvestigated for its specific toxicity to cancer cells at high concentrations only achievable by intravenous infusion. Here, the pharmacokinetics of vitamin C appears to change from zero to first order, displaying a constant and dose-independent half-life. The present chapter examines the pharmacokinetics of vitamin C under various conditions and discusses its implications for vitamin C homeostasis.