Specialized cytoskeletons play many fascinating roles, including mechanical integrity and wound-healing in epidermal cells, cell polarity in simple epithelia, contraction in muscle cells, hearing and balance in the inner ear cells, axonal transport in neurons, and neuromuscular junction formation between muscle cells and motor neurons. These varied functions are dependent upon cytoplasmic networks of actin microfilaments (6 nm), intermediate filaments (10 nm) and microtubules (23 nm), and their many associated proteins. In this chapter, I review what is known about the cytoskeletons of intermediate filaments and their associated proteins. I focus largely on epidermal cells, which devote most of their protein-synthesizing machinery to producing an extensive intermediate filament network composed of keratin. Recent studies have shown that many of the devastating human disorders that arise from degeneration of this cell type have as their underlying basis either defects in the genes encoding keratins or abnormalities in keratin IF networks. I discuss what we know about the functions of IFs, and how the link to genetic disease has enhanced this understanding.