Fentanyl is a synthetic opioid that was engineered to provide a potent analgesic effect, with its medical utility widely established in clinical contexts such as pain management and anesthesia. Fentanyl use has become a critical public health issue due to diversion for misuse and to rapidly proliferation of illicit manufacturing. This persistent increase in illicitly manufactured fentanyl distribution shows no indication of decline, raising significant concerns regarding its impact on public health and opioid misuse trends, including a dramatic increase in overdose deaths. Moreover, individuals from socially or economically precarious backgrounds, as well as those suffering from mental health disorders, are particularly vulnerable, as limited access to resources and support systems can lead to increased substance use as a coping mechanism for stress and adversity. Therefore, the objective of this narrative review is to provide a holistic overview on fentanyl, addressing its synthesis process, pharmacology and clinical use, relationship with gut microbiome, epidemiology and global distribution, patterns of use and motivations, and overdose treatment. For this purpose, current and relevant evidence on fentanyl and its correlates has been conscientiously assessed and outlined.