This review is part of a thematic series on adipocyte signaling in the cardiovascular system, including articles on adipose tissue, inflammation, and cardiovascular disease; diabetic cardiomyopathy; adipocyte signaling and lipid homeostasis; adipocyte signaling and the vasculature; and PPARγ activation and effects on the vasculature. The article discusses the role of adipose tissue in systemic inflammation, which contributes to obesity-associated vasculopathy and cardiovascular risk. Adiponectin, a secreted protein from adipocytes, is highlighted as a potential cardioprotective agent due to its anti-inflammatory properties. Obesity is associated with increased local adipose inflammation, which contributes to systemic inflammation and cardiovascular disease. Adipose tissue is not typically considered an immune organ, but it produces inflammatory factors that contribute to systemic inflammation. Obesity is linked to increased systemic inflammation, which is associated with increased cardiovascular risk. Weight loss reduces systemic inflammation and improves cardiovascular outcomes. Systemic inflammation is associated with increased cardiovascular risk, and inflammatory factors such as CRP, IL-6, and TNF-α are involved in cardiovascular disease progression. Mechanisms of cardiovascular pathology by systemic inflammation include atherosclerosis, hypercholesterolemia, hypercoagulability, and insulin resistance. CRP is a key inflammatory marker associated with cardiovascular risk, and its levels are elevated in obesity. PAI-1, a regulatory protein of the coagulation cascade, is elevated in obesity and contributes to a hypercoagulable state. TNF-α contributes to vasculopathy through its role in insulin resistance and systemic inflammation. IL-6 is involved in inflammation and atherosclerosis, and its levels are elevated in obesity. Angiotensinogen and angiotensin II contribute to hypertension and atherogenesis. VEGF is elevated in obesity and contributes to vascular remodeling and atherogenesis. Leptin is involved in obesity-associated hypertension and insulin resistance. SAA3 is an acute-phase reactant that contributes to atherogenesis. Adiponectin is an anti-inflammatory protein that plays a role in cardiovascular health. Obesity is associated with increased visceral adipose tissue, which contributes to systemic inflammation and the metabolic syndrome. Cardioprotective therapies such as PPARγ agonists and ACE inhibitors have anti-inflammatory effects that reduce cardiovascular risk. Statins have anti-inflammatory effects that reduce cardiovascular risk. Anti-inflammatory processes targeting adipose tissue may be a promising therapeutic approach for cardiovascular disease.This review is part of a thematic series on adipocyte signaling in the cardiovascular system, including articles on adipose tissue, inflammation, and cardiovascular disease; diabetic cardiomyopathy; adipocyte signaling and lipid homeostasis; adipocyte signaling and the vasculature; and PPARγ activation and effects on the vasculature. The article discusses the role of adipose tissue in systemic inflammation, which contributes to obesity-associated vasculopathy and cardiovascular risk. Adiponectin, a secreted protein from adipocytes, is highlighted as a potential cardioprotective agent due to its anti-inflammatory properties. Obesity is associated with increased local adipose inflammation, which contributes to systemic inflammation and cardiovascular disease. Adipose tissue is not typically considered an immune organ, but it produces inflammatory factors that contribute to systemic inflammation. Obesity is linked to increased systemic inflammation, which is associated with increased cardiovascular risk. Weight loss reduces systemic inflammation and improves cardiovascular outcomes. Systemic inflammation is associated with increased cardiovascular risk, and inflammatory factors such as CRP, IL-6, and TNF-α are involved in cardiovascular disease progression. Mechanisms of cardiovascular pathology by systemic inflammation include atherosclerosis, hypercholesterolemia, hypercoagulability, and insulin resistance. CRP is a key inflammatory marker associated with cardiovascular risk, and its levels are elevated in obesity. PAI-1, a regulatory protein of the coagulation cascade, is elevated in obesity and contributes to a hypercoagulable state. TNF-α contributes to vasculopathy through its role in insulin resistance and systemic inflammation. IL-6 is involved in inflammation and atherosclerosis, and its levels are elevated in obesity. Angiotensinogen and angiotensin II contribute to hypertension and atherogenesis. VEGF is elevated in obesity and contributes to vascular remodeling and atherogenesis. Leptin is involved in obesity-associated hypertension and insulin resistance. SAA3 is an acute-phase reactant that contributes to atherogenesis. Adiponectin is an anti-inflammatory protein that plays a role in cardiovascular health. Obesity is associated with increased visceral adipose tissue, which contributes to systemic inflammation and the metabolic syndrome. Cardioprotective therapies such as PPARγ agonists and ACE inhibitors have anti-inflammatory effects that reduce cardiovascular risk. Statins have anti-inflammatory effects that reduce cardiovascular risk. Anti-inflammatory processes targeting adipose tissue may be a promising therapeutic approach for cardiovascular disease.