Lipases are widely used in the modification of fats and oils with applications in the production of structured triacylglycerols, selective isolation or incorporation of specific fatty acids, and in oleochemistry for the synthesis of emollient esters and sugar fatty acid esters. Despite the numerous examples for the effective use of lipases, the biocatalysts often need to be optimized to show the desired specificities, stability, operational properties, etc. Beside rather classical methods such as variation of the solvent system or carrier for immobilization, the use of protein engineering methods to modify the protein on a molecular level is an important tool for the creation of tailor-designed enzymes. Protein design is also complemented with the efficient isolation of novel lipases from the metagenome. This article covers concepts and examples for the discovery of novel lipases and their variants by protein engineering and metagenome techniques.