Ligand-based virtual screening is a widespread method in modern drug design. It allows for a rapid screening of large compound databases in order to identify similar structures. Here we report an open-source command line tool which includes a substructure-, fingerprint- and shape-based virtual screening. Most of the implemented features fully rely on the RDKit cheminformatics framework. VSFlow accepts a wide range of input file formats and is highly customizable. Additionally, a quick visualization of the screening results as pdf and/or pymol file is supported.