Modern high resolution Cryo Electron Microscopy (cryo-EM) techniques are providing crucial insights into the structure of macromolecular assemblies both ex situ and within cells (in situ structural biology). While well behaved protein samples can routinely yield atomic resolution structures in single particle cryo EM experiments, key challenges arise with dynamic complexes, or with respect to proteins that fail to readily yield suitable cryo-preserved samples. In this presentation I will discuss how hybrid approaches, including the application of ‘omics technologies, can be used in the analysis of low resolution EM datasets.