This paper reviewed the literature on leptin, whose levels depend on fat stores and changes in energy balance due to fasting and overfeeding, and its consequences on the cardiovascular system. The topics covered were leptin signalling, leptin signalling in the central nervous system, leptin and the cardiovascular system, leptin resistance in the cardiovascular system, and leptin antagonists. The paper’s primary goal was to summarize the current knowledge on how leptin signalling in obesity is tied to obesity-related cardiovascular disease.