It is well acknowledged that tyramine acts as the biosynthetic intermediate precursor for octopamine. This fact has biased the interpretation of biological effects of tyramine towards an artifact of it being a partial agonist on octopamine receptors. Over recent years there has been an accumulation of evidence to show that tyramine is in fact a neuroactive chemical in its own right, with diverse physiological/behavioral roles. In addition, tyramine plays a unique role in a non-neuronal tissue, namely the Malpighian tubules. This review examines this evidence, taking into account the criteria that need to be satisfied in order to claim neuroactive chemical status. Thus, the evidence points to tyramine being synthesized by, and present in, neurons; capable of being released from neurons; removed by high affinity plasma membrane transporters; acting upon specific tyramine receptors; and producing physiological/behavioral effects that can be blocked by antagonists. This composite evidence is strong, although the final proof still awaits analysis on a uniquely identifiable tyraminergic neuron as has been possible with octopamine.