Abstract: Methods and compositions for targeting of pharmaceuticals or other therapeutics to specific tissues using tissue-specific endothelial membrane proteins are provided. The compositions comprise a therapeutic complex composed of a ligand, a linker, and a therapeutic moiety, where the therapeutic moiety can enter the cell. The ligand can be an antibody or other molecule that binds to a tissue-specific protein on the endothelial membrane of a specific tissue. The ligand need not activate a receptor, but may activate endocytosis. The therapeutic moiety can be a drug, gene, antisense oligonucleotide, contrast agent, protein, toxin, or any type of molecule that acts on the specific tissue. The linker can be a liposome or a cleavable or noncleavable chemical molecule. Alternatively, the linker may simply be the bond between the ligand and the therapeutic moiety. Alternatively, a lipophilic prodrug may be cleaved and may enter the cell due to its lipophilic properties.