A number of different cell types contribute to the cellular architecture of fat tissue. While the fat cell is functionally making important contributions to the systemic metabolic well-being, several additional cell types contribute a supportive role to bestow maximal flexibility on the tissue with respect to many biosynthetic and catabolic processes. These support cells include endothelial cells that make up blood vessels, a host of immune cells as well as adipocyte precursor cells and fibroblasts. Combined, these cell types give rise to a tissue with remarkable flexibility with respect to expansion and contraction, optimizing the ability of fat tissue to act as an endocrine organ through the release of many protein factors that critically influence systemic lipid homeostasis, as well as biochemically contributing many metabolites. The adipocyte has morphed into a cell type whose complexity we only start to appreciate. While excess adipose tissue can be harmful and is epidemiologically associated with increased rates of diabetes, cardiovascular disease, kidney disease and cancer, we now also appreciate the beneficial aspects that adipose tissue conveys, protecting us from “lipotoxic” exposure. Excess lipids in the system need to be effectively scavenged and neutralized. Healthy adipose tissue can fulfill this role very well, unhealthy adipose tissue fails to so. As such, obesity is a “protective” mechanism that allows us to store excess calories in a professional lipid storing cell type rather than spilling these lipids into other organs, such as the liver, where they wreck havoc. Unhealthy adipose tissue struggles with the imposed stress brought about by excess caloric intake. In this context, we have learned a great deal how we can define healthy adipose tissue expansion with well-vascularized fat pads that are minimally fibrotic and minimally inflamed, with larger numbers of smaller fat cells rather than fewer but bigger fat cells.