Ankyrin repeat (ANK) is a widely used sequence motif in organisms. An individual ankyrin repeat has an L-shaped structure consisting of a β hairpin followed by two α helices, namely β₂α₂ pattern. These ANK repeats form a compact domain stabilized through hydrogen-bonding interaction and hydrophobic stacking. Massive of structurally similar but functionally diverse proteins containing ANK repeats can be formed by virtue of assembly of the tandem array motifs. The central role of ANK repeat is to mediate protein-protein interaction, so that proteins can make sophisticated functions by interacting with a variety of ligands. This review focuses on structure, function and related diseases of the ANK repeats and their complexes from several members of the ANK family.