General rules for the optimization of different biocatalytic systems in various types of media containing organic solvents are derived by combining data from the literature, and the logarithm of the partition coefficient, log P, as a quantitative measure of solvent polarity. (1) Biocatalysis in organic solvents is low in polar solvents having a log P < 2, is moderate in solvents having a log P between 2 and 4, and is high in apolar solvents having a log P > 4. It was found that this correlation between polarity and activity parallels the ability of organic solvents to distort the essential water layer that stabilizes the biocatalysts. (2) Further optimization of biocatalysis in organic solvents is achieved when the polarity of the microenvironment of the biocatalyst (log P-i) and the continuous organic phase (log P-cph) is tuned to the polarities of both the substrate (log P-s) and the product (log P-p) according to the following rules: vertical bar log P-i - log P-s vertical bar and vertical bar log P-cph - log P-p vertical bar should be minimal and vertical bar log P-cph - log P-s vertical bar and vertical bar log P-i - log P-p vertical bar should be maximal, with the exception that in the case of substrate inhibition log P-i should be optimized with respect to log P-s. In addition to these simple optimization rules, the future developments of biocatalysis in organic solvents are discussed.