This paper uses the theoretical and empirical contributions of recent international literature on the determinants of long run economic growth to explain the historical origin of the enormous regional economic inequalities which characterize Colombia. The results indicate that geography and culture are not direct determinants of differences in regional per capita income. Nevertheless, geography did play a central but indirect role through its influence on settlement patterns during the colonial period. Although econometric estimations indicate that the colonial legacy influenced contemporary differences in regional income, it is not clear if this effect operates via the institutions or human capital.