Some matrix chemicals used in MALDI mass spectrometry are not sufficiently vacuum‐stable and therefore not suitable for extended MALDI imaging experiments. Caging the MALDI matrices by covalent attachment of a photocleavable group renders them vacuum‐stable, as reported by Qiuqin Zhou et al. in their Research Article (e202217047). The caged matrix is eventually uncaged in situ by the UV laser in the MALDI ion source. Thereby, the original matrix is liberated, thus enabling MALDI imaging of large clinical or pharmacological sample cohorts. Artwork by Miriam Rittel, Stefano Rizzo, and Silas Ackermann.