Interleukin (IL)-6 is a pleotropic cytokine with various physiological and pathophysiological functions in different cells and tissues. In cells residing within white adipose tissue, several, and sometimes conflicting, IL-6 actions have been described in the development of obesity-associated derangements of glucose metabolism. Herein, we aim to summarize opposing findings and discuss recent evidence that IL-6 signaling in adipose tissue is regulated in a depot and cell-specific manner.