In recent years there has been an intensification of demands for independence on the part of many subnational regions in Western and other countries. The literature concerning these movements has tended to neglect systematic investigation of the economic aspects of separatism in favor of noneconomic issues. This paper focuses on the actual and potential economic advantages and disadvantages implicit in separation. Numerous specific cases are used to illustrate the general arguments. The conclusions, though strongly qualified, tend to support the position that it is not unreasonable to expect an increase in regional economic well-being if separation occurs in many of the cases examined. While the central issue is not likely to be decided on purely economic grounds, clarification of the economic issues should at least enhance the rationality of the decision-making process.