There is an extensive research base on obesity treatment and on the health benefits of weight loss, but relatively little research has focused on obesity prevention. This article summarizes results of a workshop conducted by investigators funded under a National Institutes of Health initiative designed to stimulate novel research for obesity prevention. The 20 pilot studies funded under this initiative involved study populations that were diverse with respect to life stage and ethnicity, were conducted in a variety of natural and research settings, and involved a mix of interventions, including face-to-face group and individual counseling, as well as mail, telephone, and internet-based approaches. The workshop, which occurred approximately halfway through the 3-year funding period, emphasized concepts and experiences related to initiating and conducting obesity prevention studies. Investigators discussed theoretical perspectives as well as various challenges encountered, for example, in study implementation in different clinical and community settings, in working with children and families, and in studying pregnant and postpartum women. Other topics discussed included the difficulty of motivating individuals for prevention of weight gain, relevant cultural and racial/ethnic considerations, and the particular need for valid and practical measures of energy balance, body composition, and physical fitness in obesity prevention research. A key conclusion was that using obesity treatment as the primary paradigm may be a limiting perspective for considering obesity prevention issues. Further insights derived from the workshop deliberations are reflected in a detailed list of recommendations for future obesity prevention research.