<p>The Quest for Orthologs has focused on identifying orthologs from the perspective that they are more likely to have retained function over a given evolutionary distance than paralogs (or xenologs) have, enabling the transfer of functional annotation. It has become clear that function is defined by biochemistry that is under selective pressure. Quantitative descriptions of function are available within this framework and may offer understanding that is not provided by more qualitative descriptions of function. Changes in selected biochemistry, mutational processes, and selective strength can all lead to quantitative changes in function. This is discussed for proteins that have been subjected to gene duplication and for proteins that have evolved simply through the speciation process.</p>