The use of herbaria for science and conservation is revolutionizing the discovery, exploration, and protection of biodiversity at unprecedented scopes and scales. The Global Metaherbarium—a digitally interlinked, open-access resource—is stimulating these efforts and helping to facilitate massive investigations that utilize aggregated digital derivatives of physical herbarium specimens. Simultaneously, the growing use of this virtual resource is expanding the use of physical collections by researchers from many scholarly domains who increasingly are sampling specimens for multiomic investigations (e.g., genomics, transcriptomics, metabolomics, proteomics, and microbiomics). These investigations are leading to new scientific insights and supporting the development of conservation actions, but they come with a substantial cost: the (partial) destruction of priceless and often irreplaceable specimens, which constitute a global heritage that should be permanently safeguarded for future reference. The absence of a comprehensive set of “best practices” for destructively sampling herbarium specimens leads to confusion and uncertainty from researchers and institutions alike and risks over-exploitation of precious collections when the research is executed. Here, we provide a set of best practices aimed at reducing these uncertainties and creating a framework for sustainably and ethically sampling herbarium specimens. Our recommendations are intended for two complementary but overlapping audiences—users and stewards—who together build, use, and protect herbarium collections.