Purpose: To compare the operating modes of the Holmium:YAG laser and Thulium fiber laser. Additionally, currently available literature on Thulium fiber laser lithotripsy is reviewed. Materials and methods: Medline, Scopus, Embase, and Web of Science databases were searched for articles relating to the operating modes of Holmium:YAG and Thulium fiber lasers, including systematic review of articles on Thulium fiber laser lithotripsy. Results: The laser beam emerging from the Holmium:YAG laser involves fundamental architectural design constraints compared to the Thulium fiber laser. These differences translate into multiple potential advantages in favor of the Thulium fiber laser: four-fold higher absorption coefficient in water, smaller operating laser fibers (50-150 µm core diameter), lower energy per pulse (as low as 0.025 J), and higher maximal pulse repetition rate (up to 2000 Hz). Multiple comparative in vitro studies suggest a 1.5-4 times faster stone ablation rate in favor of the Thulium fiber laser. Conclusions: The Thulium fiber laser overcomes the main limitations reported with the Holmium:YAG laser relating to lithotripsy, based on preliminary in vitro studies. This innovative laser technology seems particularly advantageous for ureteroscopy and may become an important milestone for kidney stone treatment.