Recently, the endocrine activity of adipose tissue cells has been intensively studied. In effect, a wide range of exported secretory proteins, dubbed adipokines, have been identified as constituents of the adipose proteome (adipokinome). Besides their effects on glucose and energy metabolism, adipokines are potent modulators of inflammation. This chapter provides a state-of-the-science review of adipokine-mediated paracrine signaling that may be implicated in the pathogenesis of inflammation-related diseases such as atherosclerosis, thyroid-associated ophthalmopathy, and breast cancer. We also point out a possible contribution of adipose tissue-associated mast cell secretory activity to the development of these diseases. Finally, we provide arguments for yin-yang (protective vs pathogenic) roles of adipokines in inflammation. This hypothesis may provide further novel drug targets for the development of adipopharmacology of inflammatory diseases.