Neuropsychiatric disturbances stemming from infectious diseases are widespread in both the industrialized world and developing countries. Such neuropsychiatric syndromes are not necessarily the result of infectious processes directly involving the central nervous system, they may also be complications of systemic infections. There are many microbial, viral, and parasitic agents, as well as other types of infectious substances, which can affect the central nervous system, leading to the appearance of neurological and psychiatric symptoms that may cause suffering to the patient, and even be disabling. When considering the psychiatric manifestations of infectious illness, it is important to consider clinical manifestations derived from a possible systemic infection, which can be less obvious than a direct involvement of the central nervous system. Acute organic reactions may accompany many systemic infections, especially at the extremes of life. A clear example is the delirium that frequently occurs with pneumonia in the elderly. In these clinical syndromes, several factors could be responsible for the alterations in cerebral metabolism. The mere fact of having a fever could be involved. Cerebral anoxia often appears to be responsible, or the influence of toxins derived from the infecting micro-organism. More complex metabolic disturbances or the accumulation of toxic intermediate products can also be -implicated. Likewise, infections that course as chronic or subacute illnesses are frequently accompanied by the onset of depressive syndromes. One of the factors implied in clinical depression that occurs within the context of systemic infectious illnesses (e.g. tuberculosis and infectious mononucleosis), is a sense of physical vulnerability, possibly heightened by a loss of strength and negative changes in the patient's appearance. Patients are often afraid of losing their earning capacity or even their jobs, as well as other social and occupational problems associated with the illness. Another very important factor, above all with the human immunodeficiency virus (HIV) and other sexually transmitted disease (STD), is the social stigma that these patients may suffer. Sexually transmitted disease infection implies sexual activity that historically carries connotations of illicit, casual, sexual encounters, and acquiring an STD is frequently associated with embarrassment and social stigma. In addition to the disease itself, the medications commonly used to treat infectious illnesses can have side-effects that alter patients’ behaviour, as well as their cognitive and affective functioning (Table 5.3.5.1). In this chapter we consider infections of clinical interest in the practice of psychiatry. These conditions will be dealt with briefly, and textbooks of general medicine should be consulted for further details. Prion diseases and chronic fatigue syndromes, which are also related to the subject of the present chapter, are discussed in Chapters 4.1.4 and 5.2.7, respectively.