Due to the breakthrough in the technologies of cryo-EM, atomic models of many macromolecules are now available from their better than 4 A cryo-EM maps. To respond to this revolution, we offer this course that covers the review on X-ray crystallography, the historical development of cryo-EM, the theory of EM image formation and analysis, current breakthrough including the hardware of direct electron camera and the software that can disentangle solution conformations. Finally, we will engage students with hands on practice on making EM specimen, plunger-freezing, and image processing using RELION and other software.