Obesity has been at the forefront of the public health agenda in the United States since the late 1990s. Commonly considered a simple condition of excess for most of the 20th century, I argue that in order for scientific inquiry into obesity to be considered legitimate, an important transformation was required: obesity needed to be reconstructed as a complex condition, in need of multidisciplinary collaboration and significant, sustained research investment. Drawing on document analysis, in-depth interviews with obesity researchers, and ethnographic observation, in this article I show how the frame of complexity has been instrumental for obesity researchers carving out a legitimate area of scientific inquiry. I trace how complexity has been mobilized over the past 60 years, first during infrastructure building activities that occurred beginning in the early 1970s, as well as field expansion activities that institutionalized the frame during the 1990s and 2000s. While the complexity frame has largely been successful in attracting sustained investment in biomedical and public health research on obesity, it has differentially benefited researchers and those impacted by obesity.