VSFlow is an open-source command-line tool built on top of the RDKit  for the ligand-based virtual screening of large compound libraries (databases). It includes a substructure-based, a fingerprint-based and a shape-based virtual screening tool. Additionally, it provides a tool to prepare databases for screening (molecule standardization, fingerprint and conformer generation). Screenings can be parallelized with Python’s built-in multiprocessing package. Additionally, VSFlow accepts a wide range of input file formats. The screening results can be exported in various file formats, including Excel files. As additional feature, VSFlow supports the visualization of the screening results as PDF file and/or PyMOL file , allowing for a quick inspection of the results by the user. VSFlow is fully written in Python.