Pyrogens are fever-and inflammation-causing agents that cause serious health hazard, especially in the case of intravenous drugs and pharmaceutical products. While lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria remains the prototypic pyrogen, substances such as lipoteichoic acid (LTA) and peptidoglycan from Gram-positive bacteria and others are increasingly recognized as potent immune stimuli. The presence of pyrogens in the body initiates secretion of pro- inflammatory cytokines by monocytes. When high concentrations of pyrogens enter the blood stream they cause fever, septic shock or even death. The presence of small amounts of endotoxin in recombinant proteins preparations can cause side effects in host organism such as endotoxin shock, tissue injury, and even death. Due to these reactions, it is essential to remove endotoxin from drugs, injectables, and other biological and pharmaceutical products. Depyrogenation refers to the removal of pyrogens from solutions, most commonly from injectable pharmaceuticals. A depyrogenation study is the key biological test, in addition to thermometric tests, for the qualification of depyrogenation devices. Depyrogenation can be defined as the elimination of all pyrogenic substances, including bacterial endotoxin, and is generally achieved by removal or inactivation. Depyrogenation, like sterilization, is an absolute term that can only be theoretically demonstrated because of test insensitivity. Because virtually all new materials involved in a production process, including factory employees, can be potential sources of pyrogen contamination, raw material screening and depyrogenation can often go a long way to ensure that final products are free from pyrogens and does not require costly removal of or inactivation of pyrogen. The current review provides a detailed discussion of the theoretical concept and mechanism of depyrogenation