Beyond their role as macronutrients, nonesterified fatty acids (free fatty acids, FFAs) and their derivatives (prostanoids and eicosanoids) serve as signaling molecules regulating a variety of processes including inflammation, metabolism, and gene expression. While traditionally considered only to be esterified with coenzyme A staging the lipid for phospholipid and triacylglycerol biogenesis, unesterified fatty acids can diffuse laterally in the plasma membrane and interact with receptors thereby providing metabolic opportunities to elaborate a variety of second messenger systems. Receptors for fatty acids (CD36/SR-B2, GPCRs), prostaglandins (DP/EP receptors) and leukotrienes (LT receptors) are abundantly expressed by fat cells and are themselves controlled lipid signaling. Moreover, such receptors are variably expressed in different adipose depots implying specificity of signaling systems, particularly in white adipose tissue versus brown or beige fat. This chapter will summarize our current awareness of fatty acid receptors expressed by adipocytes and the signaling pathways that are affected downstream of lipid binding.