Aromatic solvents and oil-soluble amphiphiles are recognized as asphaltene precipitation inhibitors in oil production and transportation. In the absence of the model describing the effect of these inhibitors on asphaltene precipitation from crudes, proposed is a thermodynamic micellization model explaining the inhibition mechanism for both aromatic solvents and oil-soluble amphiphiles. The model shows that aromatic solvents are concentrated in the micellar shell, and the interfacial tension between the asphaltene micellar core and shell is reduced as the micelles becomes stabler. A crude, mixed with a small amount of an oil-soluble amphiphile, achieves a high micellar stability. The amphiphiles behave like resin species of the crude and coadsorb onto the micellar core with resins. The adsorption enthalpy of an amphiphile onto the micellar core is much higher than that of the resin and, therefore, amphiphiles can be very effective inhibitors. The results suggest that the adsorption enthalpy data can be used to screen the amphiphiles for asphaltene precipitation inhibition. For a given oil-soluble amphiphile, this model can predict the amount of the amphiphile required to inhibit the precipitation.