Uricase, commonly known as urate oxidase, is an enzyme that catalyzes the conversion of uric acid into allantoin, carbon dioxide, and hydrogen peroxide. In humans, the lack of functional uricase results in the buildup of uric acid, which can lead to hyperuricemia and related health issues such as gout, kidney stones, and tumor lysis syndrome (TLS). A promising approach to address this issue is the utilization of microbial uricase as a therapeutic agent. Microbial sources of uricase offer significant therapeutic potential due to its economical production and versatility, allowing for modifications that can improve its stability and effectiveness in medical applications. This chapter explores the chemistry of uric acid, the diversity of microbial uricase producers, and the intricate pathways involved in uric acid degradation. It also delves into the genetic regulation of uricase expression and the factors influencing its activity. Beyond its biological significance, microbial uricase has far-reaching applications in diagnostics, agriculture, and industrial bioremediation. In medicine, it offers innovative solutions for treating hyperuricemia and gout, with new nanozyme-based therapies holding high promise. This chapter underscores the transformative potential of microbial uricase, paving the way for advanced therapeutic applications and sustainable industrial practices.