With the rise of the opioid epidemic, the practicing neurologist must recognize the patterns of a growing number of opioid-associated neurological injuries. This is in addition to the classic toxidrome of miosis, altered mental status, and respiratory depression, which must never be overlooked, as it is reversible and potentially lifesaving. Several other idiosyncratic syndromes due to opioid-related nervous system insults are defined by their characteristic imaging findings and portend variable functional recovery. Opioid toxicity can not only lead to brain injury, but also spinal cord and, rarely, peripheral nerve injury. As several newer synthetic opioids are undetectable by most assays, a low threshold to suspect opioid exposure must be maintained.