Polyunsaturated acyl chains play an important role in human biology. These lipids cannot be synthesized de novo and they are selectively distributed to certain organs and are found predominantly only in certain lipid classes. Their selective distribution is a consequence of the specificity of the binding of these lipids by certain proteins. Lipoxygenases are a group of well studied enzymes that specifically oxidize polyunsaturated fatty acids. We propose that certain features of the interaction of lipoxygenases with polyunsaturated acyl chains are also found in other unrelated proteins that act on lipids with these moieties. The features common to several of the enzymes that specifically interact with polyunsaturated acyl chains include the fact that the polyunsaturated chain is drawn out of the membrane to bind to a hydrophobic channel within the protein and that a similar pattern of required amino acids residues comprises part of the binding site for the polyunsaturated chain. This article is part of a Special Issue entitled: Protein Folding in Membranes.