For a good performance in Clinical and Forensic Toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. This manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. Particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administration, candidiasis, wounds associated with anthrax or clostridium contaminated heroin, desomorphine related lesions and characteristic non-biological evidences are some commonly reported findings in opioids abuse, which will be discussed. For this purpose, clinical and forensic cases from our database (National Institute of Legal Medicine and Forensic Sciences, North Branch, Portugal), in addition to literature data, are reviewed.