Glutathione (GSH) is essential across all kingdoms of life, playing critical roles in cysteine metabolism, protection against cell stress, control of cellular redox levels and facilitation of various signaling pathways. Gram-negative bacteria use a dedicated ABC transport system to import GSH. Understanding how GSH accumulates in Gram-positive bacteria has come primarily from studies of Streptococcus mutans, commonly found in dental plaque. S. mutans can make its own GSH, but it also imports GSH to create intracellular concentrations v25 times higher than those attained from de novo synthesis. Despite the importance of GSH, there is limited information on the cellular machinery required for its import in Gram-positive bacteria. To address this, Vergauwen, Savvides and colleagues have investigated the function of SMU_1942c from S. mutans (referred to as GshT). Previous work revealed that this protein was required for GSH assimilation. Now, the authors find that GshT preferentially binds GSH and also displays affinity for GSH variants. The crystal structure of GshT in complex with glutathione disulfide (GSSG) reveals a bilobed structure with the ligand-binding site lying in the deep cleft between the two lobes. As with other solute-binding proteins, GSSG-bound GshT is in a closed conformation and probably undergoes a Venus flytrap–like conformational change when it binds ligand. Close inspection of the binding pocket explains how GshT can bind a variety of GSH derivatives. The protein makes intimate contacts with the first glutamyl moiety of GSSG, reflecting how it would capture GSH, while forming only a few specific interactions with the second. Additional studies using a gsht mutant confirm that GshT is responsible for GSH import in S. mutans. The authors further show that GshT primes import through TcyABC, an ABC transporter previously associated with import of L-cystine, a source of intracellular cysteine. This dual import pathway may become an attractive target for controlling S. mutans virulence. (Mol.Microbiol.http://dx.doi.org/10.1111/mmi.12274,publishedonline23May2013)