This Review considers the driving roles for innate immune cells in the adipose tissue in the lean state (A), obesity (B) and upon weight loss (C) with respect to the mediators produced by these cells, their cross-talk with the adaptive immune system as well as the influence of intercellular communications with the brain, skeletal muscle, the gut, particularly the small intestine, and the liver. As these inflammatory mediators are most likely produced/released by multiple different types of innate immune cells, as well as cells of the adaptive immune system, this Figure does not attribute roles for one cell type to expression of specific mediators in the overall environment of metabolic perturbation triggered by obesity.