Obesity is a major public health issue, and its trend is increasing worldwide. Interventions to effectively treat obesity and its related diseases are advocated. Given the complexity of obesity management, nurses need specific core skills to work in the Obesity Clinic and can act as key players in the multidisciplinary team of the Obesity Clinic. To provide practical guidelines for nurses working in Obesity Clinic for effective management of obesity and its related diseases, the current evidence on the role nurses in the obesity clinic was reviewed. Nurses can play a pivotal role in the management of patients with obesity and associated diseases that may require a stricter follow-up than usual care. Given the complexity of the treatment of obesity and its comorbidity, nurses should receive a specific training for: 1) methods and tools to effectively treat obesity and obesity-related disease; 2) patients and families education on nutrition, lifestyle changes, and prevention/management of obesity-related diseases; 3) motivation of patients towards adherence to treatment to achieve their specific goals. This review highlights the need of specific core skills for nurses working in the Obesity Clinic.