Toxin-induced leukoencephalopathy is a rare neurological condition that has been previously associated with intracranial radiation, chemotherapy, drugs of abuse, and environmental exposures. Herein, we present a patient with brain-biopsy proven toxin-induced leukoencephalopathy, likely secondary to multiple environmental offenders including insecticides and non-Food and Drug Administration approved anabolic steroids, opioids, and benzodiazepines. A 60-year-old man presented to our service as a direct transfer from an outside facility for evaluation of a rapidly progressive neuropsychiatric decline. Extensive workup with blood work, cerebrospinal fluid analysis, paraneoplastic panel, serial magnetic resonance imaging brain with and without contrast, and electroencephalograms were unrevealing. Magnetic resonance imaging brain showed diffuse confluent white matter disease, which was non-specific. The patient was treated with high-dose methylprednisolone and trials of intravenous immunoglobulin without any significant improvement. Finally, a brain biopsy was performed, and pathology confirmed a spongiform leukoencephalopathy, favoring a toxin-related etiology. The diagnosis of toxin-induced leukoencephalopathy should be considered in patients with steep neuropsychiatric decline and associated diffuse white matter disease. Diagnosis relies heavily on history of exposure, clinical presentation, imaging findings, and ultimately, histopathology from brain biopsy. The recognition of the clinical presentation is important to pursue the appropriate diagnostic workup and treatment.