Lanthanide-doped nanoparticles exhibit unique luminescent properties, including large Stokes shift, sharp emission bandwidth, high resistance to optical blinking, and photobleaching, as well as the unique ability to convert long-wavelength stimulation into short-wavelength emission. These attributes are particularly needed for developing luminescent labels as alternatives to organic fluorophores and quantum dots. In recent years, the well-recognized advantages of upconversion nanocrystals as biomarkers have been manifested in many important applications, such as highly sensitive molecular detection and autofluorescence-free cell imaging. However, their potential in multiplexed detection and multicolor imaging is rarely exploited, largely owing to the research lagging on multicolor tuning of these particles. Lanthanide doping typically involves an insulating host matrix and a trace amount of lanthanide dopants embedded in the host lattice. The luminescence observed from these doped crystalline materials primarily originates from electronic transitions within the [Xe]4f(n) configuration of the lanthanide dopants. Thus a straightforward approach to tuning the emission is to dope different lanthanide activators in the host lattice. Meanwhile, the host lattice can exert a crystal field around the lanthanide dopants and sometimes may even exchange energy with the dopants. Therefore, the emission can also be modulated by varying the host materials. Recently, the advance in synthetic methods toward high quality core-shell nanocrystals has led to the emergence of new strategies for emission modulation. These strategies rely on precise control over either energy exchange interactions between the dopants or energy transfer involving other optical entities. To provide a set of criteria for future work in this field, we attempt to review general and emerging strategies for tuning emission spectra through lanthanide doping. With significant progress made over the past several years, we now are able to design and fabricate nanoparticles displaying tailorable optical properties. In particular, we show that, by rational control of different combinations of dopants and dopant concentration, a wealth of color output can be generated under single-wavelength excitation. Strikingly, unprecedented single-band emissions can be obtained by careful selection of host matrices. By incorporating a set of lanthanide ions at defined concentrations into different layers of a core-shell structure, the emission spectra of the particles are largely expanded to cover almost the entire visible region, which is hardly accessible by conventional bulk phosphors. Importantly, we demonstrate that an inert-shell coating provides the particles with stable emission against perturbation in surrounding environments, paving the way for their applications in the context of biological networks.