The synthesis and chemical properties of a variety of chemically modified calix[4]pyrroles are described. The effects of structural changes, specifically the presence and absence of substituents on the meso-like and beta-pyrrolic carbons, on anion affinities are detailed as is their effect on macrocycle conformation. Also described are unsymmetrical systems, bearing an aliphatic and aromatic substituent on each of the four meso-like carbon atoms. In this case, the properties of the resulting configuration isomers are discussed in terms, again, of the resulting effects oil macrocycle conformation and substrate binding affinity. Finally, the use of appropriately functionalized calix[4]pyrrole systems as rudimentary fluorescence-based anion sensors is presented.