Obesity has become a major health problem which frequently is associated with the development of chronic diseases including type 2 diabetes and cardiovascular disease. It is now accepted that adipose tissue is one of the major endocrine organs and both non-adipocytes and adipocytes contribute to the secretory output of adipose tissue. By releasing an unexpected diversity of signaling and mediator molecules, adipose tissue communicates with other tissues, such as liver, skeletal muscle, the heart, and vasculature. In this review we focus on adipocytes and the adipokinome secreted by these cells. In obesity, enlargement of adipocytes has been linked to a dysregulation of adipokine secretion and adipose tissue inflammation. This switch to a chronic state of low-grade-inflammation represents a critical pathogenic link between obesity and the development of multifactorial diseases, like type 2 diabetes and the metabolic syndrome. Because of the relevance of adipose tissue in the progression of these common diseases, multiple unbiased, proteomic approaches have characterized the secretome from both rodent and human adipocytes and adipose tissue. These studies have emphasized the complex nature of the adipokinome and identified hundreds of adipokines. However, the amount of overlap between the identified adipokines thus-far indicates that the adipokinome is still incompletely characterized. Using a proteomics approach, we identified 347 proteins, of which 263 were predicted to be secreted. Forty-four proteins were identified as novel adipokines and data will be presented regarding regulation and function of these novel adipokines. Most importantly, we recently reported DPP4 as a novel adipokine. This protein interferes with beta-cell function and we suggest that it may represent a potential link between obesity and the metabolic syndrome. Novel data will be presented suggesting that DPP4 initiates cellular signaling in different tissues, and thus participates in the crosstalk between fat and other organs. (This work is supported by DFG, DAAD and EFSD)