The fundamental functions of epithelia and endothelia in multicellular organisms are to separate compositionally distinct compartments and regulate the exchange of small solutes and other substances between them. Tight junctions (TJs) between adjacent cells constitute the barrier to the passage of ions and molecules through the paracellular pathway and function as a `fence' within the plasma membrane to create and maintain apical and basolateral membrane domains. How TJs achieve this is only beginning to be understood. Recently identified components of TJs include the claudins, a family of four-transmembrane-span proteins that are prime candidates for molecules that function in TJ permeability. Their identification and characterization have provided new insight into the diversity of different TJs and heterogeneity of barrier functions in different epithelia and endothelia.