Bucinnazine (1-butyryl-4-cinnamylpiperazine) is a synthetic opioid recently discovered in heroin seized samples in the U.S and in Europe. It was first synthesized in the late 1960s and has been used for the treatment of cancer-associated chronic pain in China for many years. Bucinnazine is one of the most potent compounds among the series of piperazines, which also include other relevant compounds, such as MT-45, AD-1211, and 2-methyl-AP-237, a methylated derivative of bucinnazine. Bucinnazine is considered a μ-selective opioid, binding primarily to the μ-opioid receptor. However, bucinnazine also may share several characteristics with other piperazines, which act primarily on dopamine, serotonin, and norepinephrine neurotransmission. At the present, bucinnazine is not scheduled in the U.S., as it is not a therapeutic choice for the treatment of pain. Nevertheless, with the advent of the cryptocurrency and the easy access of substances on the Darknet, bucinnazine is a real threat to the public health. This review discusses the main aspects of bucinnazine's chemistry, pharmacology, and toxicology and brings attention to the risk of the presence of this opioid in seized samples. Further studies on bucinnazine are still required to better evaluate its toxicity mechanisms, potential for drug-drug interactions, and abuse liability. Such information will be of utmost importance to guide future policies concerning the legal status of bucinnazine in the U.S.