The introduction of pathogens to new areas is a key factor in the global emergence of disease, and can result in devastating impacts on communities and ecosystems. We show how globalization, a form of anthropogenic environmental change including the global trade of goods and travel by humans is contributing to the spread of pathogens. We determined the pathway of spread for the introduction of highly pathogenic H5N1 avian influenza into 52 countries in Asia, Europe, and Africa. We integrated data on phylogenetic relationships of virus isolates, migratory bird movements, and trade in poultry and wild birds. We show that 9 of 21 of H5N1 introductions to countries in Asia were most likely through poultry, and 3 of 21 were most likely through migrating birds. In contrast, spread to most (20/23) countries in Europe was most likely through migratory birds. Spread in Africa was likely partly by poultry (2/8 introductions) and partly by migrating birds (3/8). Our analyses predict that H5N1 is more likely to be introduced into the Western Hemisphere through infected poultry and into the mainland United States by subsequent movement of migrating birds from neighboring countries, rather than from eastern Siberia. These results highlight the potential synergism between trade and wild animal movement in the emergence and pandemic spread of pathogens and demonstrate the value of predictive models for disease control. Finally, we show how trade and travel increase the probability of West Nile virus being introduced into Hawaii, Galapagos and Barbados.