Native state mass spectrometry (MS) has been recognised as a rapid, sensitive, and high throughput method to directly investigate protein-ligand interactions for some time, however there are few examples reporting this approach as a screening method to identify relevant protein-fragment interactions in fragment-based drug discovery (FBDD). In this paper an overview of native state MS will be presented, highlighting the attractive properties of this method within the context of fragment screening applications. A summary of published examples using MS for fragment screening will be described and reflection on the outlook for the future adoption and implementation of native state MS as a complementary fragment screening method will be presented.