With the recent explosion of interest in the field of nanobiotechnology, viruses are now finding new applications in materials science and medicine. Here, we discuss the engineering of 'smart' nanoparticles that are based upon recombinant adenovirus (Ad) vectors and that combine multiple functions of targeting, imaging and drug delivery. We focus on the use of Ads as a carrier and delivery system for macromolecules other than DNA and develop the rationale behind using Ads for such applications. Due to the modular nature of the Ad capsid, multiple therapeutic or diagnostic modalities, such as the addition of magnetic resonance imaging contrast agents, radiation sensitizers and antigenic peptides for vaccines, can be incorporated by modifying different sites on the viral capsid. These types of particles have a tremendous potential to increase the sensitivity and specificity of therapies. © 2009 Elsevier Ltd. All rights reserved.