The LIM domain is a zinc finger structure that is present in several types of proteins, including homeodomain transcription factors, kinases and proteins that consist of several LIM domains. Proteins containing LIM domains have been discovered to play important roles in a variety of fundamental biological processes including cytoskeleton organization, cell lineage specification and organ development, but also for pathological functions such as oncogenesis, leading to human disease. The LIM domain has been demonstrated to be a protein–protein interaction motif that is critically involved in these processes. The recent isolation and analysis of more LIM domain-containing proteins from several species have confirmed and broadened our knowledge about LIM protein function. Furthermore, the identification and characterization of factors that interact with LIM domains illuminates mechanisms of combinatorial developmental regulation.