Endotoxin is an integral component of the outer membrane of Gram-negative bacteria and a prime example of unique and highly conserved bacterial surface molecules that engage with the innate immune system of the mammalian host via pattern recognition receptors on a range of host cells. The results of this interaction, which may be beneficial or detrimental to the development and welfare of the host, are reviewed, focusing on the different sensitivities and consequences in a range of hosts of experimental exposure to endotoxin, the disease outcomes and recent developments in our understanding of the mechanisms involved.