Density functional theory (DFT) calculation is a very useful approach to study surface reactions in heterogeneous catalysis. The current chapter reviews some recent work applying this approach to Co-catalyzed Fischer–Tropsch (FT) synthesis. The chapter mainly focuses on the following fundamental issues in this system: (i) Surface chemistry of cobalt catalysts, especially under FT conditions; (ii) mechanistic study of the Co catalyzed FT process, including the chain initiation, propagation and termination; and (iii) deactivation mechanism of Co-based catalysts in the FT process.