Adipose tissue is one of the largest organs, playing important roles in physiology and pathologies of multiple diseases. However, research related to adeno-associated virus (AAV) targeting adipose tissue has been left far behind studies carried out in the liver, brain, heart, and muscle. Despite initial reports indicating poor performance, AAV-mediated gene delivery to adipose tissue has continued to rise during the past two decades. AAV8 and a novel engineered hybrid serotype, Rec2, have been shown to transduce adipose tissue more efficiently than other serotypes so far tested and have been applied in most of the in vivo studies. The Rec2 serotype displays high efficacy of gene transfer to both brown and white fat via local and systemic administration. This review summarizes the advances in developing AAV vectors with enhanced adipose tropism and restricting off-target transgene expression. We discuss the challenges and strategies to search for and generate novel serotypes with tropism tailoring for adipose tissue and develop AAV vector systems to improve adipose transgene expression for basic research and translational studies.