Single Particle Cryo Electron Microscopy (cryo-EM) developed, around 2015, into a leading field within the Structural Biology domain, when CMOS-based direct electron detectors and cryo-vitrification of sample solutions became fully available. As a result, macromolecular structures could be solved in the 2 – 4 Å resolution range, thus supporting a strong/new development in structure-to-function and mechanistic studies. The following years (to date) have seen a continuous development of cryo EM hardware (300 and 200 kV columns, new detectors), of sample preparation/vitrification strategies, of powerful software packages for data reduction, structure solution and analysis. Cryo EM is particularly suited for the study of large macromolecular complexes (proteins, nucleic acids, …), and provides probably the best straight approach to structural studies on membrane proteins once these are solubilized, paving the way to the study of this wide protein group that is the target of more than 30% of current effective drugs. Regular fibrillar protein aggregates (amyloids) have also been successfully targeted through cryo EM, further highlighting the impact of this approach on biological and biomedical research.