Obesity, a pandemic health problem, is now considered as a chronic inflammatory state, related to many autoimmune diseases, such as multiple sclerosis. Thus, adipokines, inflammatory mediators secreted by adipose tissue, play an important role modulating the immune response. In this context, obesity, especially during adolescent age, seems to be a key factor for the development of multiple sclerosis. Leptin, the main pro-inflammatory adipokine secreted by the adipose tissue, has been found increased in patients with multiple sclerosis and is able to regulate the immune system promoting a pro-inflammatory response. Leptin signaling in both innate and adaptative immune cells might have immunomodulatory effects in the context of multiple sclerosis. In this way, leptin has been found to produce a Th1 and Th17 response, increasing M1 macrophages and decreasing regulatory T cells and Th2 response. Moreover, circulating inflammatory adipokines, such as leptin, have been found in people with multiple sclerosis. In the present work, we are reviewing literature to update the body of knowledge regarding the role of obesity and leptin in multiple sclerosis.