Entrezpy is a Python library that automates the querying and downloading of data from the Entrez databases at NCBI by interacting with E-Utilities. Entrezpy implements complex queries by automatically creating E-Utility parameters from the results obtained that can then be used directly in subsequent queries. Entrezpy also allows the user to cache and retrieve results locally, implements interactions with all Entrez databases as part of an analysis pipeline, and adjusts parameters within an ongoing query or using prior results. Entrezpys modular design enables it to easily extend and adjust existing E-Utility functions.