Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS) and various other names, is a syndrome of unknown and possibly multiple etiology, affecting the central nervous system (CNS), immune, and many other systems and organs. Most definitions other than the 1991 UK "Oxford", require a number of features, the most common being severe mental and physical depletion, which according to the 1994 Fukuda definition is "unrelieved by rest", and is usually made worse by even trivial exertion (controversially the Oxford and Fukuda require this to be optional only).

However patients usually contend that they have many, often severe symptoms which are far more onerous, such as pain, muscle weakness, loss of brain function, hypersensitivity, orthostatic intolerance, immune and in some cases life-threatening cardiac and respiratory problems, and it is these symptoms exacerbated by extremely low stamina that cause greatest suffering, not "fatigue", which more properly describes a normal state of recovery unrelated to pathology. Some cases resolve or improve over time, and where available, treatments bring a degree of improvement to many others.