The Department of Health and Human Services, through the FDA's Office of Orphan Products Development, is offering funding opportunities for innovative natural history studies focused on rare diseases. This funding aims to address significant unmet needs in the field by generating high-quality data essential for medical product development. Eligible organizations, including higher education institutions, nonprofits, and government entities, can apply for grants under the R01 Research Project Grant mechanism. Funding for prospective studies can reach $400,000 per year for up to four years, while retrospective studies can receive up to $150,000 per year for two years. Key application dates include submission deadlines in early 2026 and 2028, with specific guidelines on data quality, collaboration, and patient input emphasized. The FDA encourages applicants to use innovative methods and frameworks, including effective patient engagement and standardized approaches to data collection. Successful applications will undergo a rigorous review process based on their scientific and technical merit, which is pivotal for advancing understanding in rare diseases and ensuring efficient drug development.