The idea of light sheet microscopy was already born a hundred years ago. Richard Zsigmondy used an innovative method of side illumination to observe the chemistry of nanometer sized colloids, which won him the Nobel Prize in chemistry in 1925. Almost a century later, Ernst Stelzer and his group re-implemented that technology within an era dominated by fluorescence microscopy. Fluorescent labeling of cells and the sensitivity of light sheet microscopy led to new insights into the three-dimensionality of whole organs and the four-dimensionality of developing organisms. The open source project “openSPIM” by the group of Pavel Tomancak finally made light sheet microscopy accessible to the broad scientific community. This has allowed Hartmann Harz at the Center for Advanced Light Microscopy at the LMU Munich to build an in-house light sheet microscope which PhD student Svenja Rühland from the group of Peter Nelson uses to image therapeutic vehicle cells within 3D tumor spheroids.