Ionic liquids (ILs) and their mixtures with low molecular solvents present ideal properties for use as flotation liquids in cryo-ultramicrotomy. With control of T g and η by co-solvent addition, flat, ultra-thin sections are reliably floated onto transmission electron microscopy grids even at temperatures as low as -100°C. Even more, the liquids and their mixtures are stable in the microtome trough for several hours because of low vapor pressure and low solidification temperature. Compared to established flotation media for soft polymer systems, the time and skill needed for cryo-ultramicrotomy are significantly reduced. Although just a handful of ILs are discussed and a good general choice identified, if different liquid characteristics are needed for a particular sample, thousands of additional ILs will perform similarly, giving this new approach enormous flexibility.