Cryo electron microscopy (cryoEM) has emerged as a tool of choice for determining three-dimensional (3D) structures of macromolecular complexes or biological nano-machines (>50 kDa) in their native forms. When such complexes can be isolated in microgram quantities, atomic models can now be obtained by cryoEM single-particle analysis and model building. Comparisons of atomic models obtained for the same complex at different functional states provide mechanistic insights for its functions. For pleomorphic complexes, such as those in their cellular or tissue environments, molecular resolution structures can be reconstructed by cryo electron tomography (cryoET). Examples will be presented to illustrate the power of cryoEM in visualizing 3D structures of nano-scale biological machines containing proteins, nucleic acids or lipids to inform such fundamental biological processes as genome transcription, molecular translocation and infectious diseases.