Sequence databases, such as NCBI, are a very important resource in many areas of science. Downloading small amounts of sequences to local storage can easily be performed using any recent web browser, but downloading tens of thousands of sequences is not as simple. NCBI Mass Sequence Downloader is an open source program aimed at simplifying obtaining large amounts of sequence data from NCBI databases to local storage. It is written in python (can be run under both python 2 and python 3), and uses PyQt5 for the GUI. The program can be run in either graphical or command line mode. Source code is licensed under the GPLv3, and is supported on Linux, Windows and Mac OSX. Available at https://github.com/ElsevierSoftwareX/SOFTX-D-15-00072.git, https://github.com/StuntsPT/NCBI_Mass_Downloader