The effect of surface charge on the stability of gold nanoparticles (AuNPs) to the biogenic thiols glutathione (GSH), dihydrolipoic acid (DHLA), and cysteine was quantified. It was observed that the rate of release of fluorescein-tagged ligand was determined by the surface charge of the AuNPs, with cationic particles much more labile than anionic analogues. This ability to tune stability is significant for the design of both delivery vehicles and intracellular probes.