Sodium gadolinium fluoride (NaGdF4) is an ideal host material for the incorporation of luminescent lanthanide ions because of its high photochemical stability, low vibrational energy and its ability to mediate energy exchanges between the lanthanide dopants. This protocol describes the detailed experimental procedure for synthesizing core-shell NaGdF4 nanoparticles that incorporate lanthanide ions into different layers for efficiently converting a single-wavelength, near-IR excitation into a tunable visible emission. These nanoparticles can then be used as luminescent probes in biological samples, in 3D displays, in solar energy conversion and in photodynamic therapy. The NaGdF4 nanoparticles are grown through co-precipitation in a binary solvent mixture of oleic acid and 1-octadecene. Doping by lanthanides with controlled compositions and concentrations can be achieved concomitantly with particle growth. The lanthanide-doped NaGdF4 nanoparticles then serve as seed crystals for subsequent epitaxial growth of shell layers comprising different lanthanide dopants. The entire procedure for the preparation and isolation of the core-shell nanoparticles comprising two epitaxial shell layers requires ∼15 h for completion.