The large size of lasers limits their applications in confined spaces, such as in biosensing and in vivo brain tissue imaging. In this regard, micron-sized lasers have been developed. They exhibit great potential for biological detecting, remote sensing, and depth tracking due to their small sizes, sensitive properties of their spectral fingerprints, and flexible positional modulation in the microenvironment. Lanthanide-based luminescent materials that possess long excited-state lifetime, narrow emission bandwidth, and upconversion behaviors are promising as gain mediums for novel microlasers. In addition, lanthanide-based microlasers could be generated under natural ambient conditions with pumped or continuous light sources, which significantly promotes the practical applications of microlasers. Recent progress in the design, synthesis, and biomedical applications of lanthanide-based microlasers has been outlined in this review. Lanthanide ions doped and upconverted lanthanide-based microlasers are highlighted, which exhibit advantageous structures, miniaturized dimensions, and high lasing performance. The applications of lanthanide-based microlasers are further discussed, the upconverted microlasers show great advantages for biological applications owing to their tunable excitation and emission characteristics and excellent environmental stability. Moreover, perspectives and challenges in the field of lanthanide-based microlasers are presented.