The requirements for glycolysis are examined in relation to other essential metabolic processes in the most primitive organisms. The construction of more complex enzymes from primitive domain building blocks is assessed with respect to glycolytic enzymes. Special attention is given to the evolution of the NAD binding domain in dehydrogenases and the related, frequently observed nucleotide binding domain. An attempt is made to differentiate between convergence and divergence of frequently observed domains. Consideration is given to the structure-function relation of these domains and the development of quaternary structure in later stages of evolution. Some attention is also given to the evolution of structural adaptation to extreme environments as a means of differentiating between essential functions and specific modifications.