Hemeproteins and other tetrapyrrole containing biomolecules form one of the most diverse classes of enzymes present in the natural world. Through recognition of the homologies of the active constituents of the globins, cytochromes and peroxidases (heme) as well as reaction centers and light-harvesting complexes (chlorophylls, bacteriochlorophylls, pheophytins) it is apparent that nature has evolved methods with which to utilize the same chemical cofactor for a range of disparate chemistries and enzymatic transformations, including electron transfer, small ligand binding, charge-separation and exciton transfer. The plasticity of these cofactors with respect to physicochemical modulation in complexes is particularly emphasized by heme protein reduction potentials, which exhibit an impressive range spanning 1V from -550mV to +450mV versus SHE7 and are a key-determinant of their biological functions. As an addition to the classical concepts of apoprotein cofactor control via axial ligation, H-bonding and charged residue electrostatic influences, we have advocated the structural importance of the conformational flexibility of the porphyrin macrocycle as a modulator of cofactor properties and function. For example, heme is the active cofactor for oxygen transport and storage within the body and for the incorporation of molecular oxygen in organic substrates. It is involved in the terminal oxidation (cytochrome c oxidase) and the metabolism of H2O2 (catalases and peroxidases) and catalyzes various electron transfer reactions in cytochromes. Likewise, in photosynthesis the same cofactor may function as a reaction center pigment (charge separation) or as an accessory pigment (exciton transfer) in light harvesting complexes (e.g., chlorophyll a). The aim of this project is to explore how nature can use the same chemical molecule as a cofactor for chemically distinct reactions using the concept of conformational flexibility of tetrapyrroles. Contemporary analytical methods now allow a more quantitative look at cofactors in protein complexes and the development of the field is illustrated by case studies on hemeproteins and photosynthetic complexes.