Laminins are trimeric proteins that are major components of the basement membranes that separate endothelia and epithelia from the underlying tissue. Sixteen laminin isoforms have been described, each with distinct tissue expression patterns and functions. While laminins have a critical structural role, recent evidence also indicates that they also impact the migration and functions of immune cells. Laminins are differentially expressed upon immunity or tolerance and orientate the immune response. This review will summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system. Finally, the role of the laminins in autoimmune diseases and transplantation will be discussed.