It is typically the result of workinging, mental stress, jet lag or active recreation, but also from boredom or disease, or simply lack of sleep. It may also have chemical causes, such as poisoning or mineral or vitamin deficincies.
Fatigue can also be quite dangerous when performing certain duties that require constant concentration, such as driving a vehicle. When someone is sufficiently fatigued, they may experience microsleeps that can cause them to lose concentration.
See also
In the plural, fatigues are pants of the style worn in the military.