Orthogonal arrays or assemblies of intramembranous particles (OAPs) are structures in the membrane of diverse cells which were initially discovered by means of the freeze-fracturing technique. This technique, developed in the 1960s, was important for the acceptance of the fluid mosaic model of the biological membrane. OAPs were first described in liver cells, and then in parietal cells of the stomach, and most importantly, in the astrocytes of the brain. Since the discovery of the structure of OAPs and the identification of OAPs as the morphological equivalent of the water channel protein aquaporin-4 (AQP4) in the 1990s, a plethora of morphological work on OAPs in different cells was published. Now, we feel a need to balance new and old data on OAPs and AQP4 to elucidate the interrelationship of both structures and molecules. In this review, the identity of OAPs as AQP4-based structures in a diversity of cells will be described. At the same time, arguments are offered that under pathological or experimental circumstances, AQP4 can also be expressed in a non-OAP form. Thus, we attempt to project classical work on OAPs onto the molecular biology of AQP4. In particular, astrocytes and glioma cells will play the major part in this review, not only due to our own work but also due to the fact that most studies on structure and function of AQP4 were done in the nervous system.