Here we review recent studies on the metastable fragmentation of individual DNA and RNA building blocks and their compositions using matrix assisted laser desorption/ionization mass spectrometry (MALDI). To compare the fragmentation channels of small DNA components with larger compositions we have studied the metastable fragmentation of the deprotonated nucleobases, ribose, ribose-monophoshates, the nucleosides, the nucleoside 5′-monophosphates and selected oligonucleotides. Both previously published and unpublished data are reported. To gain a comprehensive picture of the fragmentation of individual components, metastable fragmentation of native components are in many cases compared to chemically modified components and isotopic labelling is used to unambiguously identify fragments. Furthermore, to shed light on the underlying fragmentation mechanisms we complement the experimental studies with classical dynamics simulations of the fragmentation of selected compounds. For the DNA and RNA components where dissociative electron attachment studies have been conducted we compare these to the metastable fragmentation channels observed here.