Studies characterising biological variation and diversity, which are enormously valuable to science and society, have been the main use for natural history museum collections for centuries. Even with rapidly changing technologies, especially genomic techniques, traditional systematics and biogeography remain the principal collections-based disciplinary emphases for biological research programs in natural history museums. Studies relevant to modern environmental change, and biomedicine, among other major fields in the biological science, also represent important uses for museum collections, but these receive less attention within natural history museums, collections, or curator-led research programs. Very large economic and other impacts of rapidly changing environments, climates, and disease landscapes in the Anthropocene highlight a need for organized, future-focused efforts to expand natural history research programs to incorporate additional uses of collections to complement studies of systematic biology. Indeed, critical documentation of Anthropocene impacts, and the future of natural history museums, including public impressions of their relevance, may depend on it.