Nanoparticles have an advantage for molecular imaging in that many functionalities can be added to the surface and interior of the particle. This brief review focuses on the design of nanomaterials that take advantage of PET. An evolutionary approach is presented, leading to the optimization of the nanoparticle composition and structure to achieve controlled in vivo circulation and tissue-selective targeting. Organic and inorganic nanostructures are included. Nanoprobes for PET of angiogenesis and cancer are highlighted.