Chronic pain is a frequent condition that affects an estimated 20% of people worldwide, accounting for 15%-20% of doctors' appointments (Treede et al., 2015). It lacks the acute warning function of physiologic nociception, and instead involves the activation of multiple neurophysiologic mechanisms in the somatosensory system, a complex neuronal network under the control of powerful autoregulatory loops and able to undergo rapid neuroplastic alteration (Verdu et al., 2008). There is a growing body of research suggesting that some such pathways are shared by major psychologic disorders such as depression and anxiety, opening new avenues in co-treatment strategies. In particular, besides anticonvulsants, which are today used as analgesics, other psychopharmaceuticals, such as the tricyclic antidepressants, are displaying efficacy in the treatment of neuropathic and nociceptive chronic pain. The state of the art regarding the mechanisms of nociception and the pharmacology of both the neurotransmitters involved and the wide range of psychoactive compounds that may be useful in the treatment of chronic pain are discussed.