Chronic kidney disease (CKD) substantially reduces quality of life and leads to premature death for thousands of people each year. Dialysis and kidney organ transplants remain prevalent therapeutic avenues but carry significant medical, economic and social burden. Podocytes are responsible for blood filtration selectivity in the kidney, where they extend a network of foot processes (FPs) from their cell bodies which surround endothelial cells and interdigitate with those on neighbouring podocytes to form narrow slit diaphragms (SDs). During aging, some podocytes are lost naturally but accelerated podocyte loss is a hallmark of CKD. Insights into the origin of degenerative podocyte loss will help answer important questions about kidney function and lead to substantial health benefits. Here, approaches that uncover insights into podocyte mechanobiology are reviewed, both those that interrogate the biophysical properties of podocytes and how the external physical environment affects podocyte behaviour, and also those that interrogate the biophysical effects that podocytes exert on their surroundings.