The article titled Syphilis in the 21st Century: Challenges and Advances in Diagnosis and Treatment aimed to analyze the main challenges and significant advances in the diagnosis and treatment of syphilis throughout the 21st century. The research focused on understanding how new technologies and public health strategies have contributed to the improvement of disease management, as well as identifying the existing barriers. A bibliographic review was conducted to compile and synthesize relevant data from previous studies, providing a comprehensive overview of the topic. The explanatory methodology used allowed for a theoretical deepening of the issues involved in the detection and treatment of syphilis. The technical procedures included the analysis of scientific articles, health organization reports, and systematic reviews that addressed both technological advances and the challenges faced by health professionals. Among the main advances discussed were rapid tests and nucleic acid amplification tests (NAATs), which have significantly improved the ability to diagnose the infection early and accurately. Improvements in public awareness and prevention programs were also addressed. Despite the advances, the article also highlighted persistent challenges such as antibiotic resistance and difficulties in accessing effective treatments, especially in less developed regions. Benzathine penicillin G was reaffirmed as the treatment of choice, but distribution logistics and adherence to treatment remain important obstacles. The bibliographic review concluded that, for effective control of syphilis, integrated strategies that combine education, prevention, early diagnosis, and adequate treatment are necessary, as indicated in the reviewed literature.