The human and mouse genomes each contain at least 12 genes encoding LIM homeodomain (LIM-HD) transcription factors. These gene regulatory proteins feature two LIM domains in their amino termini and a characteristic DNA binding homeodomain. Studies of mouse models and human patients have established that the LIM-HD factors are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs such as the pituitary gland and the pancreas. In this article, we review the roles of the LIM-HD proteins in mammalian development and their involvement in human diseases. © Springer 2005.