This entire chapter is devoted to the esterification reactions involving compounds containing multifunctional groups like OH, COOH, CH3 and CHO. The description involves optimisation of reaction conditions for use of lipases in nonpolar solvents under low water activity by both conventional and response surface methodological conditions. It attempts to bring out the superiority of lipase catalysis over chemical synthesis in the few reactions discussed. Esterification of the OH group of lactic acid with the COOH group of few long-chain fatty acids to synthesise 2-O-alkanoyl acids is discussed in detail. This is followed by the work on the preparation of tolyl esters, protocatechuic aldehyde esters, 4-t-butylcyclohexyl acetate and acetylation of β-cyclodextrin. State of the lipases employed under nonaqueous solvents in the above-mentioned reactions is best brought by studies on thermostability and scanning electron microscopy. The role of water, constituting the micro-aqueous phase around the enzyme during its employment under nonpolar conditions, attempts to explain the integrity of the enzyme under such conditions, in terms of developing a theoretical model on the micro-aqueous pH and various equilibria occurring at and associated with the micro-aqueous phase.