This chapter summarizes recent studies employing colorimetric vesicle-based systems for biomolecular sensing. Vesicular aggregates exhibit an important advantage as a biological sensing platform in that they mimic the cell membrane-the site of molecular docking, ligand-receptor binding, and other important processes that can be exploited as a means of signal generation. Particularly attractive for sensing applications is the use of colour changes visible to the naked eye or detected spectroscopically as the signal transduction mechanism. Vesicle assemblies comprising polydiacetylene (PDA)-a chromatic polymer that undergoes blue-red transformations in response to varied biological analytes and processes-are the primary focus of this chapter. We discuss the features of PDA that make it a promising constituent in biosensing platforms, in particular its self-assembly properties, the rigid framework allowing incorporation of varied lipid constituents, and the chromatic transformations induced by reactions with biological analytes. Recent studies depicting distinct vesicle assemblies are summarized. Vesicles comprising chemically modified PDA, in which receptor units are attached to the polymer-surface head groups, have been employed for detection of chemical and biological toxins, viruses, and bacteria. Mixed vesicles in which lipid bilayer domains are incorporated within the PDA matrix have also been extensively used as colorimetric biomimetic membrane platforms for studying diverse membrane processes and cell-surface phenomena. The PDA-embedded lipid bilayers further facilitate anchoring of varied molecular markers and recognition modules.