Efficient and specific delivery of genes to the cell type of interest is a crucial issue in gene therapy. Adeno-associated virus (AAV) has gained particular interest as gene vector recently and is therefore the focus of this chapter. Its low frequency of random integration into the genome and the moderate immune response make AAV an attractive platform for vector design. Like in most other vector systems, the tropism of AAV vectors limits their utility for certain tissues especially upon systemic application. This may in part be circumvented by using AAV serotypes with an in vivo gene transduction pattern most closely fitting the needs of the application. Also, the tropism of AAV capsids may be changed by combining parts of the natural serotype diversity. In addition, peptides mediating binding to the cell type of interest can be identified by random phage display library screening and subsequently be introduced into an AAV capsid region critical for receptor binding. Such peptide insertions can abrogate the natural tropism of AAV capsids and result in detargeting from the liver in vivo. In a novel approach, cell type-directed vector capsids can be selected from random peptide libraries displayed on viral capsids or serotype-shuffling libraries in vitro and in vivo for optimized transduction of the cell type or tissue of interest.