Nanotechnology has recently allowed us to design and prepare nanoplatforms with the potential to face currently unresolved problems. Among these platforms, nanoparticles in particular are versatile objects that find applications in many different areas. In the vast ensemble of materials that have been explored to obtain nanoparticles with improved performances, we here focus our attention on lanthanide-based nanocrystals. These recently developed species are extremely interesting and well known particularly for their ability to emit anti-Stokes shifted light (upconversion) with relatively high brightness. Many advantageous characteristics of such materials are emerging, and their use as multimodal imaging agents is rapidly growing. We here survey some recent examples on this subject, mainly focusing on systems having NIR-to-NIR emission properties for in vivo applications.