Podosomes are specialized, highly dynamic adhesion structures protruding from the membrane of animal cells. Their complex ultrastructure enables interactions with the microenvironment and extracellular matrix and the sensory and mechano-effector functions. Although historically attributed to monocytes, macrophages, and dendric cells, podosomes also occur in osteoclasts, endothelial cells, muscle, neural, cancer, and other cell types. This review describes podosome structure and podosomes’ role in mechanotransduction and beyond.