The specialized cells of adipose tissue – adipocytes, are not captured by now-standard single-cell transcriptomic approaches due to their size, fragility, and unique composition. Recently, single-nucleus RNA-sequencing (sNucSeq) allows to view human adipose tissue(s), adipocytes included, at a new resolution. Beyond “atlas-ing” the cellular landscape of adipose tissue and recognizing the presence of novel adipocyte subtypes, novel questions can now be formulated and begin to be approached with sNucSeq. In this talk, insights already gained on human adipose tissue using sNucSeq will be presented. Next, sNucSeq-enabled opportunities to investigate how obesity and obesity reversal dynamically shape the diversity through which adipocytes respond (or become resistant) to hormonal ques key to adipose tissue function, as well as adipocytes’ interaction with other cell types comprising adipose tissue, will be discussed. Finally, the possibility and challenges in translating the above to the clinic, in an attempt to facilitate more personalized approaches to treat obesity and its complications will be raised.