Scientific interest in the endocannabinoid (EC) system developed as a result of the known effects of tetrahydrocannabinol, including an increased desire to consume food. Further investigation has led to the belief that the EC system plays a role in accumulation of intra-abdominal fat and worsening of cardiovascular disease (CVD) risk factors. The EC system has been identified as a neuromodulatory system that is normally inactive but can be overstimulated to cause and exacerbate numerous metabolic pathologies. EC agonists and receptors have been identified in the brain, liver, and peripheral adipose tissue, and the EC system is known to affect metabolism in these areas and others through neuromodulatory signals. Meal size, body weight, and numerous metabolic factors such as triglyceride and cholesterol levels, insulin resistance, and glucose intolerance can be affected via the EC system. Further research into the EC system is warranted to elucidate its role in metabolic homeostasis.