Folic acid supplementation during the periconceptional period is a well-established strategy to prevent neural tube defects (NTDs). However, emerging uncertainties surrounding optimal dosage, alternative folate forms, duration of use, and the role of genetic variability have sparked scientific and policy debates. In Brazil, these challenges are amplified by unique contextual factors, including the routine distribution of high-dose folic acid (5000 µg) through the public health system, social vulnerability, low adherence, and limited population-specific evidence for the country’s highly admixed population. This narrative review critically examined the scientific evidence and public health policies surrounding folic acid supplementation, with a focus on Brazil. We examined historical developments, international recommendations, and emerging controversies, including the emerging influence of misinformation. Despite the worldwide progress in NTD prevention, both local and global challenges persist, including delayed initiation, inconsistent adherence, and uncertainty regarding alternative supplementation regimens. Addressing these demands requires the development of context-specific guidelines, alongside coordinated strategies in provider training, public education, monitoring, and research investments to ensure effective, safe, and equitable folic acid supplementation.