The last decade has seen an exponential increase of protein structures solved by X-ray crystallography, NMR and cryo-electron microscopy. The existing information on the protein crystal structure and various computational design toolboxes are furnishing protein engineering more accurately than ever. Structure-based protein engineering involves the application of structural knowledge and software tools to alter protein structures and functions. Much work has been focused on enzyme structure analysis by computational tools to detect key residues responsible for specific properties. We observe that structure-based engineering techniques are potential and compatible approaches that greatly simplify the process of improving certain properties of enzymes. The molecular modeling and de novo design tools are instrumental in increasing antibody stability and binding affinity for therapeutics. They are also proven helpful in identifying epitope of antigens for vaccine development. As the recent advances in structure-guided protein engineering are summarized in the review, it is clear that the structure-based protein engineering could result in tremendous saving in time and investment compared to traditional methods.