Based on their low concentrations in mammalian brain, octopamine, β–phenylethylamine, tyramine, and tryptamine are classified as “trace” amines (TAs) and viewed as metabolic by-products. TAs are related to the classical monoamine transmitters and are synthesized from the same precursor aromatic amino acids. The recent discovery of a family of G protein-coupled receptors preferentially activated by TAs rekindled interest in TAs, but without a known circuitry, their function remains elusive and understudied. We now have anatomical evidence of an endogenous TA system in spinal cord, and show that the TAs recruit locomotor circuits and modulate ongoing locomotion. Our newest evidence suggest the TAs represent a parallel biochemical modulatory system that alters circuit function via a membrane transporter shuttling system that operates independent of synaptic actions. The long-term goal is to understand the physiological relevance of the TAs as an intrinsic modulatory system for subsequent therapeutic manipulation of spinal circuit function.