Obesity and associated metabolic co-morbidities are a worldwide public health problem. Negative health outcomes associated with obesity, however, do not arise from excessive adiposity alone. Rather, deleterious outcomes of adipose tissue accumulation are a result of how adipocytes are distributed to individual regions in the body. Due to our increased understanding of the dynamic relationship that exists between specific adipose depots and disease risk, an accurate characterization of total body adiposity as well as location is required to properly evaluate a population’s disease risk. Specifically, distinctive tissue depots within the body include the lower body, upper body and abdominal (deep and superficial) subcutaneous regions, as well as visceral (mesenteric and omental) regions. Upper body and visceral adipose tissues are highly associated with metabolic dysfunction and chronic disease development, whereas lower body gluteofemoral subcutaneous adipose tissue imparts protection against diet-induced metabolic derangement. Each adipose depot functions distinctly as an endocrine organ hence it has a different level of impact on health outcomes. Effluent from adipose tissue can modulate the functions of other tissues, whilst receiving differential communication from the rest of the body via central nervous system innervation, metabolites and other signaling molecules. More so, adipose depots contain a diverse reservoir of tissue-resident immune cells that play an integral part in both maintaining tissue homeostasis, as well as propagating metabolically-induced inflammation. Overall, the conceptualization of obesity and associated risks needs updating to reflect the complexities of obesity. We review adipose tissue characteristics that are linked to deleterious or beneficial adipose tissue distributions.