The progress in the design of hybrid photoluminescent assemblies based on upconversion nanoparticles (UCNPs) meant for biomedical applications is analyzed. The key approaches to the synthesis of bright UCNPs and their surface modification, including encapsulation into hydrophilic shells and providing with therapeutic and targeting agents, are described. The range of potential applications of UCNPs in analytical biochemistry, biomedical diagnostics and therapy of cancer and infectious diseases is considered.