The sympathetic nervous system (SNS) innervates all known organs, but its molecular and cellular organization is essentially unknown. The era of molecular genetics has made great strides in the mechanistic dissection of brain circuits as well as the immune system, but such endeavor has not yet reached the SNS. We have recently discovered a direct connection between the SNS and the adipose organ. Moreover, we found that this neuro-adipose junction mediates lipolysis and fat mass reduction. Therefore, direct and targeted activation of sympathetic inputs to adipose tissues could represent a new strategy for the induction of fat loss and, ultimately, a new anti-obesity therapy that would circumvent current therapeutic challenges such as central leptin resistance and drug delivery to the brain. We aim at discovering fundamental biological mechanisms that could render this idea possible. A key part of this is to explore the emerging link between the SNS and immunity. My lab has identified a novel population of sympathetic associated macrophages (SAMs) that appear to suppress the output of SNS neurons in fat. Moreover, we are developing molecular genetic tools to systematically establish a functional and molecular neuronanatomical map of the SNS.