In recent years, the global resurgence of syphilis has posed significant challenges to public health. This sexually transmitted infection, caused by the bacterium Treponema pallidum, can have severe consequences if left untreated, including neurological and cardiovascular complications. Diagnosing syphilis is complex due to its diverse clinical presentations, necessitating a multifaceted approach, including serological, molecular, and direct techniques such as dark-field microscopy. Penicillin remains the primary and effective treatment, but emerging macrolide-resistant strains have spurred investigations into alternative antibiotics. Syphilis vaccine development faces unique hurdles, yet promising strategies are under investigation. Targeted prevention strategies focus on high-risk populations such as men who have sex with men, pregnant women, and individuals with multiple sexual partners. The integration of syphilis services into primary healthcare enhances accessibility, early detection, and treatment. Innovative point-of-care diagnostics offer rapid, sensitive testing, while ongoing vaccine research holds the potential for long-term prevention. Addressing the global burden of syphilis requires a multifaceted approach, encompassing immunological advancements, innovative diagnostics, targeted prevention, and primary healthcare integration. Collaborative efforts between governments, healthcare systems, researchers, and communities are essential to effectively combat syphilis, striving toward a syphilis-free future that promotes better sexual health and overall well-being.
