Obesity increases the risk for a number of diseases, including type 2 diabetes, liver and cardiovascular disease, or neurological disorders. Low-grade chronic systemic inflammation typically accompanying obesity is considered driving these disorders. The inflammatory factors produced by the hypertrophic adipose tissue can have systemic effects. The present review summarizes current knowledge on the most investigated in this context, inflammatory cytokines: Tumor necrosis factor (TNF), interleukin 6 (IL6), IL1β, and interferon γ. Their metabolic effects on organs such as the liver, the skeletal muscle, the pancreas and the brain, and therapeutic interventions targeting systemic inflammation in obesity are discussed.