Another well-known type of encephalopathy associated with psychotropic drug therapy is serotonin toxicity (ST) or serotonin syndrome (SS), which is characterized by autonomic and neuromuscular symptoms and altered mental status. In contrast with the idiosyncratic nature of NMS, ST is a spectrum pathophysiological state assumed to derive from excess serotonergic neural transmission caused by serotonin-related psychotropic agents. In these two decades, pharmacotherapy with psychotropic drugs for patients with mental illness has been dramatically changed, and classical prototypal antipsychotics and antidepressants have been replaced with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs), respectively. These newly developed psychotropic drugs are generally safer and more tolerable than older drugs. However, atypical antipsychotics are not free of the risk of development of NMS, and the explosive prevalence of SSRIs prescribed not only for depression but also for a number of psychiatric diagnoses such as anxiety, eating, impulse-control, and personality disorders may increase the incidence of ST. Therefore, these two pathological states still remain as major adverse effects of psychotropic drugs involving altered functioning of the central nervous system (CNS), to which all clinicians prescribing psychoactive drugs should pay attention. The popularity of SSRIs also increased the case reports of patients with discontinuation syndrome, which sometimes includes CNS symptoms like anxiety and irritability. In this chapter, the author provides a comprehensive overview of the above- mentioned adverse effects affecting the CNS function associated with psychotropic pharmacotherapy. In addition, several other pathological conditions potentially causing encephalopathic symptoms in psychiatric patients treated with psychotropic drugs, e.g., hyponatremia, valproate-induced hyperammonemia, transient splenial lesion of the corpus callosum, and so on, are also described. Fume events on aircraft have been linked to cases of toxic encephalopathy, for example in the case of JetBlue Captain Andrew Myers, who as a result of exposure needed a cane to walk, experienced tremors and struggled to speak. In the following year, the Federal Aviation Administration revoked Myers' medical certificate; the workers compensation board agreed that Myers experienced brain damage as a result of the event. Diagnosis Rapid diagnosis is important to attempt to prevent further damage to the brain and further neurologic deficits. It is a diagnosis of exclusion, so a full work up for other possible etiologies (hepatic, uremic, infectious, oncologic) should be performed. In addition to the neurological examination, diagnostic testing could include MRI, PET or SPECT brain imaging, EEG, QEEG and most importantly, neuropsychological testing. Screening for heavy metals,