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Obesity is a major risk factor for the development of type 2 diabetes and its associated complications, representing a major socio-economic burden for healthcare systems. The worldwide prevalence of obesity doubled since 1980, and as a consequence, the number of patients with diabetes has been continuously rising with more than 450 million people suffering from this disease at the present time. Substantial progress has been made in understanding the molecular pathways leading from excessive fat accumulation to metabolic perturbations and finally diabetes manifestation as well as related comorbidities. Nevertheless, innovative treatment regimens are urgently required to cope with the epidemic increase of obesityassociated complications. This edition of the Handbook of Experimental Pharmacology aims to analyze new insights into the pathophysiology of obesity, to examine some organ alterations and perturbed inter-organ cross-talk, to decipher the complex links to diabetes and its complications, and to collect most recent information on new strategies for the prevention and treatment of obesity and diabetes. Leading experts in the field of obesity and diabetes research provide deep insights into the current state of the art and have made substantial attempts to emphasize future directions. Individual chapters address the critical role of obesity and specifically the intestine and adipose tissue for the pathophysiology of diabetes and its complications, cover different approaches of lifestyle modifications, and highlight most recent developments of novel drugs for obesity and diabetes. Indeed, for years, only a few pharmacological solutions were available for patients with obesity, but this is changing rapidly with new molecules in the academic and pharmaceutical pipelines that will be available in the near future and hopefully change patients’ lives. We are confident that the current collection of papers will contribute to a deeper understanding of the critical role of obesity for a variety of metabolic diseases, and may at the same time stimulate future discussion and decision making regarding the development of innovative drugs and therapeutic approaches.