Since its introduction during the last decade, MALDI mass spectrometry imaging (MSI) is now a routine technique in biology. Nevertheless, a missing link exists in MALDI MSI. Lipids, peptides/proteins, metabolites and drugs can easily be mapped using MALDI-MSI, but this technique has not yet been used to map the transcriptome, which includes microRNA, siRNA and other components. This latter field of research is now one of the major fields in clinical research and needs to be explored using MALDI-MSI. To investigate the transcriptome, a novel imaging technique has been developed called Tag-Mass imaging mass spectrometry. The aim of this review is to discuss this technique from its history to its place in the future of mass spectrometric imaging.