Recent breakthroughs in optical and electron microscopy have changed the fields of Cellular and Structural Biology in a most profound manner. Ever more detailed information about the inner workings of cells is becoming available, revealing stunning new insights into molecular landscapes and their biological activities, at unprecedented levels of resolution. Besides these advancements in imaging modalities, complementary in situ methods are beginning to emerge as powerful tools in modern Cellular Structural Biology approaches. Here, I discuss how recent developments in in-cell NMR, EPR and single-molecule FRET spectroscopy contribute to our understanding of basic biological processes in live cells. Specifically, I outline how these techniques provide time-resolved atomic-resolution information about intracellular protein structures and functions, which cannot be obtained with any other method at this time.