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Affirming that excess fat can be an unfavourable medical condition is definitively not an observation of great originality. In fact, in 400 BC, Hippocrates astutely observed that “sudden death was more common in those who are naturally fat than in the lean” [1]. By the contrast, the concept of targeting the adipose tissue and internal organs with increased fat content during pharmaceutical or lifestyle intervention is of great novelty. If the reduction of excess fat is still a therapeutic goal in improving a poor cardio-metabolic profile, new insights suggest the potential of improving the effectiveness of therapeutic intervention through the adiposity, not only against. In fact, there is now a compelling need of emerging therapeutic strategies targeted to the adipose tissue. The reason for the growing scientific interest into the fat is the widely-accepted acknowledgement that adipose tissue is not a silent organ, but a very active source of multiple bioactive cytokines, called adipokines. The adipocyte, mini-organ within this neglected organ, sends outputs (adipokines) and accept inputs (nuclear receptors). The adipose tissue communicates with almost all other organs through endocrine, paracrine and also autocrine interactions. Hence, both systemic and local regulations of internal organs’ function and morphology have been recently attributed to the adipose tissue. Fat tissue is also a potential great responder, by the presence of multiple receptors that can be modulated, stimulated or inhibited by drugs with different mechanisms of action and therapeutic purposes. Of additional and supportive note is the fact that the adipose tissue can now be clinically measured and quantified by simple, accurate and reliable diagnostic tools. Both biological and clinical characteristics of the adipose tissue seem to warrant a successful development of new therapeutic strategies. The concept and importance of proximity of adipose tissue to the organs is also intriguing. Intuitively, the visceral adipose tissue has been evoked as the most desirable therapeutic target. In fact, great interest has been recently focused on the visceral adiposity, namely the fat depots that surround the internal organs. The evidences supporting the visceral adiposity as independent cardio-metabolic risk factor are rapidly emerging. A body of studies suggest that the increased fat, particularly the visceral fat, may play a significant role in the development of the metabolic syndrome, a cluster of diseases apparently independent, but actually linked by common pathogenic key factors. In this Current Pharmaceutical Design issue, leading experts in clinical and bio-molecular aspects of adiposity, and its relationship with metabolic syndrome, addressed a topic of growing and exciting interest, as well as the potential use of different adipose tissue depots and organs as therapeutic targets. A systematic and detailed overview of basic and clinical aspects of adiposity-related diseases and an extremely up-to-date of the potential within targeting adipose tissue and fatty organs, are provided in this Current Pharmaceutical Design issue. Leonetti et al. [2] introduced the concept of metabolic syndrome, with its diagnostic aspects still controversial and under continue evolution. They extensively discussed the importance of regional fat distribution rather total adiposity in cardiovascular risk stratification. Waist circumference and imaging diagnostics have been evaluated as traditional and new markers of visceral adiposity. Great attention is focused on reinforce the notion that reductions in visceral adipose tissue should be a primary aim of strategies designed to reduce health risks associated with metabolic syndrome. Human adipose tissues are not only located in different anatomic compartments, but differ for embryological origin, bio-molecular properties, and therefore different therapeutic use.......