Intermediate filaments are cytoskeletal polymers encoded by a large family of differentially expressed genes that provide crucial structural support in the cytoplasm and nucleus of higher eukaryotes. Perturbation of their function accounts for several genetically determined diseases in which fragile cells cannot sustain mechanical and non-mechanical stresses. Recent studies shed light on how this structural support is modulated to meet the changing needs of cells, and reveal a novel role whereby intermediate filaments influence cell growth and death through dynamic interactions with non-structural proteins.