Obesity results from an imbalance of energy intake and energy expenditure. While the prevalence of obesity is increasing and the negative impact on public health is being recognized, highly effective and safe therapy for obesity is not yet available.This review summarizes the current state of the art in the late-stage development area of anti-obesity drugs, provides a framework for understanding the potential disparity of animal data and human disease modification for some agents, and highlights novel agents that may provide significant clinical benefits in the future.Published literature and meeting proceedings were surveyed to review the late-stage development of new anti-obesity agents.Most of the current clinical candidates for obesity treatment are targeting neurotransmitter receptors or peptide receptors. While new agents have been discovered, a significant failure rate also emerged. Rigorous scientific investigations, developing target engagement tools, and understanding any potential rodent versus human species difference will be necessary to ascertain mechanism-based efficacy and increase the probability of success.