The initial discovery of leptin, an appetite-suppressing hormone originating from fat tissue, substantially supported the idea that fat-borne factors act on the brain to regulate food intake and energy expenditure. Since then, a growing number of cytokines have been found to be released from adipose tissue, thus acting in an endocrine manner. These adipocytokines include not only, e.g., adiponectin, apelin, resistin, and visfatin, but also inflammatory cytokines and steroid hormones such as estrogens and glucocorticoids. They are secreted from their adipose depots and differ in terms of release stimuli, downstream signaling, and their action on the brain. Clearly, adipocytokines play a prominent role in the central control of body weight, and the deregulation of this circuit may lead to the development of obesity and related disorders. In this chapter, we will focus on crosstalk mechanisms and the deregulation of adipocytokines at the expression level and/or sites of central action that eventually will lead to the development and perpetuation of obesity and diabetes.