Toxic leukoencephalopathy often involves white matter tracts connecting to higher cortical functions that cause different neuropsychiatric symptoms, such as inattention, forgetfulness, dementia, coma or even death. We present a patient who had just recovered after respiratory failure and septic shock, who then developed toxic leukoencephalopathy after intravenous heroin injection. Magnetic resonance imaging (MRI) appears to be essential for making a diagnosis, because clinical history is often unreliable and manifestations are nonspecific. Treatment is mainly supportive for toxic leukoencephalopathy. Physicians and psychiatrists should take a thorough history and be alert to the complex presentations of toxic encephalopathy.