AbstractMultifunctional nanoparticles have been developed to overcome the conventional hurdles associated with the diagnosis and treatment of disease. However, there are often caveats involved with the development and clinical translation of multifunctional nanoparticles largely regarding the notion that additional functionality increases nanoparticle complexity. Here, we discuss two design concepts, a conventional approach, ‘all‐in‐one’, and introduce the concept of ‘one‐for‐all’ to suggest that multifunctionality does not necessarily result in multicomponent complex nanoparticles. This review focuses on the design concepts of all‐in‐one and one‐for‐all with examples of each approach and a discussion on the implications for clinical translation. WIREs Nanomed Nanobiotechnol 2013, 5:250–265. doi: 10.1002/wnan.1217This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease