Major constituents of the cytoskeleton and the nuclear matrix, cytoplasmic intermediate filament subunits and nuclear lamins belong to a multigene family of proteins whose function is poorly understood. It has now become a general contention that important clues to the physiological roles of these proteins may reside in their developmental and tissue-specific expression patterns, as well as their cellular organization. The present review brings into focus experimental strategies that have been developed, over the past few years, to gain insights into the cellular mechanisms regulating the molecular polymorphism and supramolecular assembly of intermediate filaments. In this context new concepts are discussed that may be pivotal for the orientation of future studies on intermediate filament proteins.