Since 1910, The Otho S. A. Sprague Memorial Institute has pursued the mission outlined by its founder: “… to investigate the causes of disease and the prevention and relief of human suffering in the City of Chicago … ” Throughout its history, the institute has identified and responded to some of the most troublesome health concerns in the community. Asthma was and continues to be one of the most intractable conditions facing Chicagoans. To address this, in 1994 the institute launched a multiyear Chicago Asthma Initiative, focusing the bulk of its annual philanthropic budget on this topic. While that amount is modest in comparison to the largess flowing from the Gates/Buffet treasury, the investment has had significant impact. First, it changed the way the local health community interacted on this topic. Secondly, it created a replicable model for asthma and other conditions. Finally, it demonstrated how a midsized foundation could make a difference.