Under the high irradiation intensities encountered in single molecule fluorescence and super resolution studies, enhanced signal stability and photostability are critical for a successful experiment. Strategies such as oxygen removal and addition of reducing agents serving as triplet quenchers, increase fluorophore photostability. Reducing agents however require a counter-oxidating agent to mitigate free radical formation. This scheme (ROXS) has been successfully used to increase photoprotection of certain fluorophores. In our current research, we use thiol-based photostabilizers that regenerate the fluorophore ground state without the need of a second additive. Here I will describe transient absorption spectroscopy studies coupled with single molecule fluorescence microscopy studies on cyanine dyes in the search of efficient, universal, thiol-based photoprotective agents that markedly enhance Cy3B, Cy5, and Cy5B performance.