Mexicali, Baja California, close neighbor to the wealthy State of California, USA, plays an important demographic, urban, industrial, and business role in the regional economy, both domestically and binationally. All this dynamism in the region has generated important economic benefits; nevertheless the lack of attention to the care of environment have entailed severe situations of contamination, especially in regional air quality. The increase in industrial, commercial, and service activities–as well as a steep rise in vehicles in poor condition–have degraded air quality in the cross-border airshed, especially on the Mexican side. In addition, the situation is exacerbated by particle and dust emissions from illegal urban burns, agricultural burns, farming, industrial activities, and unpaved roads. In addition, the emission sources by energy generation (i.e., geothermal a fossil fuel-fired power plants in Mexicali) are more and more important. The construction of natural gas –fired power plants in the Mexicali area are exclusively to serve the California energy market has occurred and is likely to continue. These power plants are among the largest single sources of air pollution in the Ca-BC border region. The airshed is in non-attainment of federal standards on both sides of the border for PM-10, ozone and CO among others. Also, cardio- respiratory morbidity and mortality rates are one of highest in this binational zone. Recommendations discussed including the need for the harmonization of data, designation of binational airsheds, harmonization of vehicle inspection and maintenance programs, and consideration of policies regarding energy production. Also to improve air quality in the Mexicali-Imperial Valley region, resources are needed to build technological infrastructure as well as human capacity and understanding, and for programs in pollution reduction. In addition, the lack of local, binationally standardized agreements and procedures are important issues that impedes the collection, ordering, reliability, and compatibility of the medical/clinical data needed in order to do local, in-depth epidemiological studies, and hinders to a great degree the opportunity to study and propose indicators that assess the region's environmental health from a cross-border perspective.