The present invention provides targeting lipids of structure (Cl) L100 - linker - L101, where L100 is a lipid, lipophile, alkyl, alkenyl or alkynyl, L101 is a ligand or - CH2CH2(OCH2CH2)pO(CH2)qCH2-ligand, 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 aicd to cells in vivo.