The cellular plasma membrane is built up by a lipid bilayer and contains a multitude of different lipids and proteins, which among other things play a central role in cellular signaling (Figure 19.1). It is well acknowledged that the different membrane molecules are highly dynamic but do not just simply diffuse freely as introduced in 1972 by the “fluid mosaic model.”¹ Rather, molecular membrane diffusion is usually restricted and hindered; that is, it shows highly anomalous diffusion patterns and only for a few molecules appears free, following free Brownian motion (e.g., Refs. 2 through 7) (Figure 19.1). For example, interactions with immobilized or slow-moving proteins lead to the local trapping of molecules, and the time to get from one point of the membrane to another is prolonged, especially on small spatial scales (e.g., Refs. 4 and 8). Similarly, the incorporation into putative domains of high molecular order leads to a local, transient slowdown (e.g., Refs. 2, 4 through 7, 9, and 10). Such slowdown may also stem from molecular crowding, since the mobility of molecules may already be retarded by the proximity to immobilized or relatively slow-moving molecules without direct interaction.¹¹ On the other hand, the influence of the cellular cytoskeleton, underlying the plasma membrane such as cortical actin, can be manifold. Proteins may transiently be arrested to the filament, thereby hindering their own mobility or, through interactions, the diffusion path of other molecules. Further, proteins that are anchored along the filament may be an obstacle for other diffusing molecules, acting like a picket or fence, and dividing the plasma membrane into compartments, whose boundaries may be hard to cross. As a consequence of this picket-fence model, molecules may show a kind of hopping diffusion with fast diffusion inside the compartments and hindered diffusion from one compartment to the next (see, for example, Refs. 3, 12, and 13). Therefore, diffusion may be fast on small spatial scales,¹⁴ but extremely slowed down on long spatial scales.^4,10 Further, hindrances of molecular membrane motility may stem from obstacles such as membrane curvature or pits, induced by the cortical actin or proteins such as clathrin or caveolin (e.g., Refs. 15 through 17).