This review discusses recent advances in protein sensing using fluorescent polyelectrolytes that are mainly water-soluble conjugated polymers. A quencher-labeled substrate or fluorophore-labeled substrate is generally used as a probe. In the presence of an enzyme, the linker between substrate and quencher/fluorophore is cleaved and fluorescence of the polymer is either ‘turned on’ or ‘turned off’. Fluorescence behavior of these conjugated polymers is highly sensitive to conformation of the polymeric chains. Since upon binding with proteins the conformation is perturbed and fluorescence is affected, these polyelectrolytes have been used to study conformational changes in proteins. The conformation-dependent fluorescence is also a limitation for these sensors in some cases and non-conjugated polyelectrolytes have been shown to provide an alternative. Copyright © 2006 Society of Chemical Industry