The advent of site-directed mutagenesis has made it possible to determine the specific contributions to stability made by a given amino acid in a protein of interest. The purpose of this is to highlight insights that have been provided by studies of such mutant proteins, with emphasis on those studies for which high-resolution structural information is available. Experience has shown that mutant proteins usually retain overall structures that are very similar to those of their wild-type parents. Nevertheless, knowledge of the structural changes that do occur at the site of the substitution, including changes in bound solvent, can be critical in understanding the properties of mutant proteins. I will explain different factors to consider to engineer a more thermostable protein than wild-type T4 lysozyme.