Obesity prevalence continues to rise globally at alarming rates, with adverse health and economic implications. In this state-of-the-art review, we provide an analysis of selected evidence about the current knowledge in the obesity literature, including a synthesis of current challenges in obesity and its determinants. In addition, we review past and current efforts to combat the obesity epidemic, highlighting both successful efforts and areas for further development. Last, we offer insights into the next steps to address the obesity epidemic and advance the field of obesity through both research and practice by (a) adopting a systems perspective, (b) fostering cross-sector and community collaborations, (c) advancing health equity, (d) narrowing the research-to-practice and research-to-policy gaps with multidisciplinary approaches, and (e) embracing complementary approaches for concurrent obesity prevention and treatment.