Lanthanide-doped upconversion nanoparticles (UCNPs) are guest-host systems with lanthanide ions as guest dispersed in a dielectric material as the inorganic host. Over the past decades, much efforts have been devoted to UCNPs in a number of biological applications due to their low toxicity, high chemical stability and high signal-to-noise ratio. Lanthanide ions distributed in conventional UCNPs with only core structures easily lose their excitation and emission energy through energy migration to the surface quenchers, weakening the emission intensities. A hierarchically designed core/shell structure may address the challenges above by blocking the emitters from the surface and surrounding quenchers. Besides, it offers not only a flexible construction by employing active shells to endow the UCNPs with new features from enhanced light harvesting and multicolor tunability to therapeutic functions, but also largely preserves the optical integrity of UCNPs. In this review, we primarily focus on recent progress in the hierarchically designed core/shell UCNPs and discussing their challenges and opportunities. We summarize several strategies to synthesize and characterize the core/shell structure and particularly highlight the unprecedented properties through regulating the core/shell structure, including light harvesting, tuning of excitation wavelength, enhancement of emission efficiency, emission color tunability, lifetime tunability and multifunctionality. Finally, we frame the future outlook of challenges and opportunities for core/shell UCNPs. (C) 2019 Elsevier Ltd. All rights reserved.