Integrated assessment (IA) modeling and research has a long history, spanning over 30 years since its inception and addressing a wide range of contemporary issues along the way. Over the last decade, IA modeling and research has emerged as one of the primary analytical methods for understanding the complex interactions between human and natural systems, from the interactions between energy, water, and land/food systems to the interplay between health, climate, and air pollution. IA modeling and research is particularly well-suited for the analysis of these interactions because it is a discipline that strives to integrate representations of multiple systems into consistent computational platforms or frameworks. In doing so, it explicitly confronts the many tradeoffs that are frequently necessary to manage complexity and computational cost while still representing the most important interactions and overall, coupled system behavior. This talk explores the history of IA modeling and research as a means to better understand its role in the assessment of contemporary issues at the confluence of human and natural systems. It traces the evolution of IA modeling and research from initial exploration of long-term emissions pathways, to the role of technology in the global evolution of the energy system, to the key linkages between land and energy systems and, more recently, the linkages with water, air pollution, and other key systems and issues. It discusses the advances in modeling that have emerged over this evolution and the biggest challenges that still present themselves as we strive to better understand the most important interactions between human and natural systems and the implications of these interactions for human welfare and decision making.