Manoalide is a potent analgesic and antiinflammatory sesterterpene isolated in 1980 from a marine sponge. The antiinflammatory activity of manoalide is due to inhibition of PLA2, through irreversible binding to several lysine residues. The binding is realized by means of the two masked aldehyde functions present in the polar part of manoalide. Of the two aldehyde groups, only that present in the g-hydroxybutenolide ring seems to be essential, since cacospongionolides, naturally occurring analogues lacking the second masked aldehyde group, were also shown to be irreversible PLA2 inhibitors. It appears that the minimum structural requirement for exhibiting manoalide-like PLA2 inhibition would be the presence in the inhibitor of functional groups able to seize the amino groups of PLA2 lysine residues with formation of stable covalent bonds. Many manoalide analogues have been isolated from marine sponges, most of them sharing PLA2 inhibitory properties. Other interesting bioactivities have also been reported for some of these compounds.