Basement membranes are specialized extracellular matrices that surround certain cell types (muscle cells, adipose cells, etc) and are present under the basal surface of cells exhibiting polarity (epithelial, endothelial and mesothelial cells). They have a unique macromolecular composition, consisting mainly of type IV collagen isoforms, laminin isoforms, entactin/nidogen, and perlecan. These components self associate and interact with each other to form networks. Other macromolecules may be found in specialized basement membranes. In this short review, the role of selected basement membrane proteins in autoimmune diseases will be highlighted. As an example, Goodpasture's syndrome will be presented and the relatively long quest for identification of the antigenic epitope on specific domains of the alpha3(IV)NC1 will be summarized. Chagas disease will be discussed as an example of laminin-mediated autoimmunity, with emphasis on the role of sugar-based antigenic epitope(s) will be presented. Immune-mediated tubulointerstitial nephritis will be introduced and the role of a synthetic peptide in detecting proximal tubule damage in acute renal failure will be discussed. Auto-immune diseases where other basement membrane macromolecules are involved will be mentioned. Finally, the importance of understanding the functions served by domains at close proximity to the antigenic epitope(s) will be highlighted.