Although we are still discovering factors that influence the development of obesity, the vast majority of obesity research continues along this line, with less effort involved in understanding obesity reversal. Because many of the manipulations including genetic, lesion, endocrinectomy and even diet are, to at least some extent, not completely reversible, we have been studying the complete reversibility of a naturally-occurring seasonal obesity in Siberian hamsters. This work, and supportive work by others using different species including humans, ultimately has led to the view that the sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) is the principal initiator of lipid mobilization in mammals and likely all vertebrates. This notion is based on incontrovertible neuroanatomical evidence of sympathetic innervation of WAT including definitions of the CNS origins of this innervation using viral tract tracers, neurochemical evidence based on studies of sympathetic drive (norepinephrine turnover studies) and functional evidence based on the blockade of lipid mobilization by surgical or chemical sympathetic denervation. In addition, a role of the SNS in controlling fat cell proliferation was found using selective chemical denervation that triggered adipocyte proliferation. Convincing evidence for the parasympathetic innervation of WAT is missing; however, irrefutable neuroanatomical evidence of the sensory innervation of WAT exists based on viral tract tracing and markers for sensory nerves in WAT, with suggestive functional data showing that selective sensory nerve destruction blocks feedback to the CNS of the degree of adiposity. Collectively, these data demonstrate bidirectional communication between WAT and the CNS to control WAT.