INTRODUCTION: Nontreponemal tests (NTT) constitute a significant method in syphilis detection, playing a crucial role in screening, diagnosing, and monitoring disease activity. However, recent discussions have cast doubt on the traditional belief that NTT are suitable for evaluating treatment efficacy, as inconsistencies between NTT results and syphilis treatment outcomes have been observed with some frequency. AREAS COVERED: We have delineated the current status of serological methods for evaluating the therapeutic efficacy of syphilis treatment and summarized and discussed the exploration of biomarkers for syphilis therapy. A literature search was conducted in PubMed over all available dates for relevant published papers and conference abstracts with the search terms, 'Syphilis,' 'Treponema pallidum,' 'Serofast,' 'Treatment efficacy evaluation,' 'Nontreponemal,' 'RPR,' 'TRUST,' 'VDRL,' 'Neurosyphilis,' 'Pregnant syphilis,' 'Congenital syphilis,' 'Reinfection,' 'Cardiolipin,' 'Serology.' EXPERT OPINION: Currently, the assessment of treatment efficacy through serological methods is limited to the use of the NTT. Therefore, it is imperative for clinicians to gain a deeper understanding of the significance and limitations of the NTT, as well as a focus on exploring more potential indicators for evaluating treatment efficacy.