BioDynamic Imaging delivers better drug assessment in three-dimensional (3D) living tissue samples, revealing a comprehensive phenotypic response that is more physiologically meaningful than from conventional 2D or monolayer screens. Our technique is label-free and probes up to 1 mm deep in living tissue to study drug response in heterogeneous tissue environments. BioDynamic Imaging converts all forms of functional cellular motions into contrast maps of cellular mechanisms of action.