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Structural determination of protein assemblies in their native environment is essential to understand the molecular mechanisms that regulate cellular processes. This is crucial for basic research in cell biology, but it also impacts other fields such as protein engineering and drug development. However, technical constraints prevent resolving structural details at high resolution directly in the cell, whereas in vitro methods are limited to study protein complexes withdrawn from their functional context. Fundamental insight such as structural dynamics that mediate proteins' function remains largely unexplored. The challenge relies on determining the physiological architecture and dynamism of cellular molecules at high resolution. This chapter presents an overview of the dominant techniques for the structural determination of molecular assemblies …