Animal communication signals are regulated by multiple hormonal axes that ensure appropriate signal targeting, timing, and information content. The regulatory roles of steroid hormones and many peptide hormones are well understood and documented across a wide range of vertebrate taxa. Two recent studies have reported a novel function for leptin, a peptide hormone central to energy balance regulation: regulating communication signals of weakly electric fish and singing mice. With only limited evidence available at this time, a key question is just how widespread leptinergic regulation of communication signals is within and across taxa. A second important question is what features of communication signals are subject to leptinergic regulation. Here we consider the functional significance of leptinergic regulation of animal communication signals in the context of both direct and indirect signal metabolic costs. Direct costs arise from metabolic investment in signal production, while indirect costs arise from the predation and social conflict consequences of the signal’s information content. We propose a preliminary conceptual framework for predicting which species will exhibit leptinergic regulation of their communication signals and which signal features leptin will regulate. This framework suggests a number of directly testable predictions within and across taxa. Accounting for additional factors such as life history and reproductive strategies will likely require modification or elaboration of this model.