Protein lipidation is a crucial protein modification involving the attachment of hydrophobic carbon skeletons (C:14-C:60) of various lipid classes--fatty acids, sterols, glycero-, phospho- and glycolipids. The lipid-protein bond frequently (i) involves the N- or C-terminal ends of the target, (ii) requires amide, ether or ester bonds to a small aminoacid, usually Gly or Cys and (iii) depends on proteolytic events. Lipidation results in protein targeting to the membrane, with the protein behaving as a peripheral component and being oriented toward the inside or outside of the cell. The addition of a single lipid is not sufficient for membrane targeting and another signal, often involving additional lipidation, is required. The methods available for predicting lipid modifications to proteins highlight the importance of identifying short protein motifs in a field in which few data are currently available, due to the complex nature of the modification. Full proteome annotation is already feasible with these predictive tools. We show that lipidation may affect 2-4 percent of all proteins in a given proteome and that double-lipidation is widespread.