This review provides an overview of the molecular and cellular biology of intermediate filaments (IFs), which are prominent components of the cytoskeleton and nuclear envelope in eukaryotic cells. IF proteins are highly heterogeneous, with over 30 protein chains per mammalian species, and they form a complex family of proteins with a common tripartite structure: a central α-helical rod domain, and amino- and carboxyl-terminal end domains. The review discusses the distribution of IF and IF-like proteins, their structure, assembly, and regulation. It highlights the hierarchical progression from the structure of the IF protein chain to the dynamic organization and functions of IF in cells. The review also explores the evolutionary origins and complexity of IF genes, their linkage and chromosomal localization, and the regulation of IF gene expression, particularly in developing tissues. The authors emphasize the importance of understanding the functions of IF in cells, which are likely to be mediated by the hypervariable end domains of the constituent chains.This review provides an overview of the molecular and cellular biology of intermediate filaments (IFs), which are prominent components of the cytoskeleton and nuclear envelope in eukaryotic cells. IF proteins are highly heterogeneous, with over 30 protein chains per mammalian species, and they form a complex family of proteins with a common tripartite structure: a central α-helical rod domain, and amino- and carboxyl-terminal end domains. The review discusses the distribution of IF and IF-like proteins, their structure, assembly, and regulation. It highlights the hierarchical progression from the structure of the IF protein chain to the dynamic organization and functions of IF in cells. The review also explores the evolutionary origins and complexity of IF genes, their linkage and chromosomal localization, and the regulation of IF gene expression, particularly in developing tissues. The authors emphasize the importance of understanding the functions of IF in cells, which are likely to be mediated by the hypervariable end domains of the constituent chains.