For decades, the potential beneficial effect of vitamin C on human health-beyond that of preventing scurvy-has been subject of much controversy. Hundreds of articles have appeared either in support of increased vitamin C intake through diet or supplements or rejecting the hypothesis that increased intake of vitamin C or supplementation may influence morbidity and mortality. The chemistry and pharmacology of vitamin C is complex and has unfortunately rarely been taken into account when designing clinical studies testing its effect on human health. However, ignoring its chemical lability, dose-dependent absorption and elimination kinetics, distribution via active transport, or complex dose-concentration-response relationships inevitably leads to poor study designs, inadequate inclusion and exclusion criteria and misinterpretation of results. The present review outlines the differences in vitamin C pharmacokinetics compared to normal low molecular weight drugs, focusses on potential pitfalls in study design and data interpretation, and re-examines major clinical studies of vitamin C in light of these.