This feature article highlights the recent advances on the chemical synthesis, surface modification and applications of rare earth fluoride nano-/microcrysals. In the past decade, great progress in the size and shape control of rare earth fluoride nano-/microcrystals has been made by developing solution phase-based methods such as thermal decomposition, hydro(solvo)thermal reaction, hydrothermal in situ conversion route, and ionic liquids-based synthesis. The main challenge of fluoride nanocrystals for biological applications is that it is hard to obtain ideal nanocrystals with smaller size (sub-50 nm), higher luminescence yield, better dispersity and stability in aqueous solvents, and superior biocompatibility. In order to overcome these shortcomings, a series of strategies of surface modification have been outlined in this review. Finally, we introduce the application of rare earth fluorides, with special emphasis on β-NaY(Gd)F4:Yb3+, Er3+ upconversion nanopaticles (UCNPs) in biomedical applications including biological labels, multimodal bioimaging, photodynamic therapy and drug delivery.