Lysosomes are essential acidic cytoplasmic membrane-bound organelles in human cells that play a critical role in many cellular events. A comprehensive understanding of lysosome-specific imaging can ultimately help us to design robust organelle-targeting therapeutic reagents for various underlying human diseases. Luminescent lanthanide molecular materials serve as an important and upcoming class of probes for cellular imaging applications with unique luminescent photophysical features such as sharp emission profiles from the visible to near-infrared spectral regions, long decay lifetimes, attractive quantum yields, large Stokes shifts, and a low propensity to photobleaching. For the last few years, a wide variety of lysosome-targeting luminescent lanthanide probes have been engineered and utilized for the imaging of hypochlorous acid and nitric oxide at the sub-cellular level and these advances are summarized in this review. The design strategies of lanthanide molecular probes, co-localization detection and lysosomal probity assay methods are briefly highlighted. Finally, the future challenges in the development of lysosome-targeting luminescent lanthanide complexes are outlined and emphasized to inspire the design of a new generation of organelle-targeting metal complexes.