Obesity is a global epidemic that poses a serious health concern due to it being a risk factor for life-threatening chronic diseases, such as type 2 diabetes, cancer, and cardiovascular diseases. Pharmacotherapy remains the mainstay for the management of obesity; however, its usefulness is limited due to poor drug efficacy, non-specificity and toxic side effects. Therefore, novel approaches that could provide insights into obesity and obesity-associated diseases as well as development of novel anti-obesity treatment modalities or improvement on the existing drugs are necessary. While the ideal treatment of obesity should involve early intervention in susceptible individuals, targeted nanotherapy potentially provides a fresh perspective that might be better than the current conventional therapies. Independent studies have shown improved drug efficacy by using prohibitin (PHB)-targeted therapy in obese rodents and non-human primates, thus providing a proof of concept that targeted nanotherapy can be a feasible treatment for obesity. This review presents a brief global survey of obesity, its impact on human health, its current treatment and their limitations, and the role of angiogenesis and PHB in the development of obesity. Finally, the role and potential use of nanotechnology coupled with targeted drug delivery in the treatment of obesity are discussed.