The study of adipose tissue has received considerable attention due to its importance not just in maintaining body energy homeostasis but also in playing a role in a number of other physio logical processes. Beyond storing energy, adipose tissue is important in endocrine, immunological, and neuromodulatory functions, secreting hormones that participate in the regulation of energy homeostasis. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favoring the secretion of deleterious adipocytokines that induce a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases and even some types of cancer. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity, with emphasis on hypocaloric diets and exercise. The aim of this review is to examine the pathophysiological mechanisms of obesity, considering the relationship among adipose tissue and two aspects that contribute positively or negatively to keeping a healthy body homeostasis, namely, exercise and noninfectious diseases. We conclude that the relationship of these aspects does not have homogeneous effects among individuals. Nevertheless, it is possible to establish some common mechanisms, like a decrease in pro-inflammatory markers in the case of exercise, and an increase in chronic inflammation in non-communicable diseases. An accurate diagnosis might consider the particular variables of a patient, namely their molecular profile and how it affects its metabolism, routines, and lifestyle; their underling health conditions; and probably even the constitution of their microbiome. We foresee that the development and accessibility of omics approaches and precision medicine will greatly improve the diagnosis, treatment, and successful outcomes for obese patients.