BackgroundBiopharmaceutical companies face multiple external pressures. Shareholders demand a profitable company while governments, nongovernmental third parties, and the public at large expect a commitment to improving health in developed and, in particular, emerging economies. Current industry commercial models are inadequate for assessing opportunities in emerging economies where disease and market data are highly limited. ObjectiveThe purpose of this article was to define a conceptual framework and build an analytic decision-making tool to assess and enhance a company’s global portfolio while balancing its business needs with broader social expectations. MethodsThrough a case-study methodology, we explore the relationship between business and social parameters associated with pharmaceutical innovation in three distinct disease areas. The global burden of disease–based theoretical framework using disability-adjusted life-years provides an overview of the burden associated with particular diseases. The social return on investment is expressed as disability-adjusted life-years averted as a result of the particular pharmaceutical innovation. Simultaneously, the business return on investment captures the research and development costs and projects revenues in terms of a profitability index. ConclusionsThe proposed framework can assist companies as they strive to meet the medical needs of populations around the world for decades to come.