Frozen section diagnosis provides critical information for immediate surgical management decision making. Over the last several years, there have been some significant advances in treatment of genitourinary cancer, particularly with regard to surgical techniques. These changes in turn impact the type and frequency of intraoperative frozen section requests. In this review, we describe the main indications and diagnostic challenges of frozen section diagnosis during surgeries of each genitourinary organ system including prostate, kidney, bladder, testis, and penis. The pitfalls and approaches to different diagnostic situations are discussed. It is also stressed that pathologists must not only be familiar with the histological diagnosis, but also understand the limitations of frozen section diagnosis and communicate with urologists during the intraoperative treatment decision making process.