This scheme describes possible control mechanisms for CySS/GSH that contribute to redox health, generalized from the finding that CySS/GSH is an independent predictor of CAD death outcome after control for all other known risk factors. (1) CySS is cleared from plasma by xCT⁻ and other transport systems. No direct pharmacokinetic analyses are available for CySS clearance, but indirect estimates show an apparent volume of distribution equal to the total body water. This implies that plasma CySS is a surrogate for whole body thiol/disulfide oxidation status. (2) Within tissues, Trx and GSH-dependent systems have low levels of CySS reductase activity [94], and recently, a Trx-related protein, Trp14, has been identified as a CySS reductase [95]. The kinetic characteristics of this system suggest that it may become saturated and have limited capacity at high physiologic concentrations of CySS. GSH is the major low molecular weight cellular thiol antioxidant that is synthesized from the amino acid cysteine in two ATP-requiring steps. The first step catalyzed by glutamate–cysteine ligase forms γ-Glu-Cys and the second catalyzed by GSH synthetase produces GSH. The first step is rate limiting with feedback inhibition of enzyme activity by GSH and transcriptional regulation by the Nrf2 system [92]. (3) GSH release from tissues occurs through ubiquitous Mrp (multidrug resistance-associated proteins) family transporters [187]. GSH release is concentration dependent and affected by multiple factors [187]. The present interpretation is that GSH in plasma provides a surrogate for tissue NADPH supply. NADPH is used to reduce GSSG to GSH and thereby maintain plasma GSH concentrations. GSH in human plasma is metabolized by two interconnected pathways, one involving hydrolysis by γ-glutamyltransferase (GGT) and dipeptidases to form Cys, which is oxidized to CySS, and the other involving thiol–disulfide exchange with CySS to form glutathione–cysteine disulfide, which is then hydrolyzed to form CySS [23,188]. CySS/GSH in plasma is correlated to CAD death outcome [7]. Not shown: Cys export from cells occurs at rates greater than GSH export, but plasma Cys/CySS redox potential is insufficient to reduce GSSG to GSH; Cys is generated from Met at rates greater than GSH synthesis; rates of Cys incorporation into protein exceed rates of GSH synthesis; rates of GSSG reduction to GSH exceed rates of GSH synthesis [189].