The present invention provides targeting lipids of structure L.sup.100--linker--L.sup.101 (CI), where L.sup.100 is a lipid, lipophile, alkyl, alkenyl or alkynyl, L.sup.101 is a ligand or --CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.pO(CH.sub.2).sub.qCH.sub.2-liga- nd, p is 1-1000, and q is 1-20. In addition, the invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo.