Peroxynitrite (ONOO−, PN) is a biologically reactive species that is generated by the coupling reaction of nitric oxide (˙NO) and superoxide (O2˙−) radicals at diffusion-controlled rates of ∼10 M−1 s−1. The complex oxidation and nitration biology of PN and their broad implications in human disease and health provide motivation for developing new methods to detect PN in living systems. Several fluorescent probes have been synthesized and applied to detect PN in living cells. One disadvantage however is their relatively short excitation and emission wavelengths (∼550 nm), which render them difficult to employ for sensing and imaging PN in deep tissues and living animals. The other major drawback of these probes is their irreversibility in responding to PN. To solve these problems, near-infrared, reversible fluorescent probes have been developed that selectively respond to PN over other reactive oxygen species. This chapter reviews the design, synthesis, characterization and imaging applications of two cyanine-based, selenium/tellurium modulated fluorescent probes for PN.