Obesity, a major healthcare issue, is associated with significant cardiovascular morbidities, including hypertension and atherosclerosis. Numerous intensive studies conducted this decade have revealed that adipose tissue is a major endocrine organ that secretes a variety of bioactive substances, termed adipocytokines. Adipocytokine secretion profiles are altered as obesity develops, which may increase the risk of obesity-related cardiovascular disorders. For instance, leptin is upregulated in obese subjects and plays important roles in the pathophysiology of obesity-related atherogenesis through multiple mechanisms, such as its proliferative, proinflammatory, prothrombotic, and prooxidant actions. In contrast, adiponectin, which is downregulated in obese subjects, has protective effects against cardiovascular disorders at various atherogenic stages. In addition to these factors secreted by adipose tissue, neuronal circuits involving autonomic nerves are now being recognized as an important metabolic regulatory system and have thus attracted considerable attentions. Alterations in fat accumulation in intraabdominal organs, such as visceral adipose tissue and the liver, send afferent neuronal signals to the brain, leading to modulation of sympathetic tonus and thereby affecting the vasculature. Moreover, these humoral and neuronal signaling pathways communicate with each other, resulting in cooperative metabolic regulation among tissues/organs throughout the body. Further elucidation of these regulatory systems is anticipated to lead to new approaches to devising therapeutic strategies for the metabolic syndrome.