There is currently no microscopy technique that qualifies as in vivo and non-invasive… or is there? It had been a long winding road, but diffusion MRI combined with biophysical modelling may just fill that role. In this talk, we will (i) go through the latest developments and validation steps of relevant models for quantifying white and gray matter microstructure, (ii) cover their recent applications to a range of diseases, highlighting the added value of diffusion-derived microstructure metrics to disentangle pathological events and trajectories, and (iii) take a fresh look at the potential of diffusion functional MRI to detect brain activity, as an alternative to conventional contrasts that rely on neurovascular coupling.