Encapsulating DNA within degradable delivery vehicles such as micro- or nanospheres provides an effective way to protect the DNA from the surrounding environment prior to delivery. The ability to target these vehicles directly to the cell type of interest provides a way to enhance the overall efficiency of DNA delivery. One means of highly specific cell targeting is through the addition to the vehicle surface of ligands that bind specifically to receptors on the surface of the targeted cell type. Covalent conjugation of ligands to the surface of degradable delivery vehicles can be difficult, as the most commonly used vehicle formulations use materials selected for their general chemical inertness. This chapter describes methods for overcoming this, enabling encapsulation of DNA within degradable microspheres made of a commonly used biomaterial and then covalently conjugating ligands to the surface of these microspheres.