The prevalence of overweight and obesity is increasing worldwide. The physiological mechanisms involved in body weight regulation are complex and incompletely understood. Increasing evidence suggests that obesity is a multifactorial disease where many, if not all, organs of the body are involved. The adipose tissue was considered as a simple fat accumulation for a long period of time. However, nowadays it is fascinating to progressively discover its involvement in hormonal, inflammatory or immune system dysregulation. Adipokines and cytokines are involved in control and regulation of appetite and energy balance, glucose and lipid metabolism, neuroendocrine function, reproduction, immunity, and cardiovascular function. The inflammatory background associated with obesity is closely related to insulin resistance. Moreover, the inhibitory effect of endocannabinoids on the expression of adiponectin could be involved in insulin resistance. Gut microbiota related factor may be responsible for the development of diet-induced obesity and diabetes through metabolic endotoxemia which triggers the inflammatory tone. Based on recent research, several physiopathological mechanisms involved in the development of obesity are reviewed.