Information from natural history collections (NHCs) about the diversity, taxonomy and historical distributions of species worldwide is becoming increasingly available over the Internet. In light of this relatively new and rapidly increasing resource, we critically review its utility and limitations for addressing a diverse array of applications. When integrated with spatial environmental data, NHC data can be used to study a broad range of topics, from aspects of ecological and evolutionary theory, to applications in conservation, agriculture and human health. There are challenges inherent to using NHC data, such as taxonomic inaccuracies and biases in the spatial coverage of data, which require consideration. Promising research frontiers include the integration of NHC data with information from comparative genomics and phylogenetics, and stronger connections between the environmental analysis of NHC data and experimental and field-based tests of hypotheses.