The quality and future of human existence are directly related to the condition of our natural environment, but we are damaging the environment. Scientific evidence has mounted a compelling case that human behavior is responsible for deterioration in the Earth’s natural environment, with the rate of deterioration predicted to increase in the future. Acknowledging this evidence, the governments of 192 countries have formally agreed to take action to resolve problems with the climate system, one of the most highly stressed parts of the natural environment. While the intention is clear, the question of how best to proceed is not. The research reported here undertook a three-phase approach of selecting, analyzing, and synthesizing relevant literature to develop a holistic, transdisciplinary, integrative framework for IT-enabled business transformation. The focus on business transformation is because business is recognized as being a critical contributor in realizing the challenges of environmental sustainability due to its potential capacity for innovation and change—locally, nationally, and globally. This article also serves as a resource base for researchers to begin to undertake significant information systems and multidisciplinary work toward the goal of environmental sustainability. Through selection and analysis of illustrative examples of current work from 12 academic disciplines across 6 core categories, the framework addresses the key issues of uncertainty: (1) What is meant by environmental sustainability? (2) What are its major challenges? (3) What is being done about these challenges? (4) What needs to be done?