The compartmentalization of the plasma membrane is essential for cells to perform specialized biochemical functions, in particular those responsible for intracellular and intercellular signaling pathways. Study of membrane compartmentalization requires state-of-the-art imaging tools that can reveal dynamics of individual molecules with high spatial and temporal resolution. In addition, quantitative analyses are employed to identify transient changes in molecule dynamics. In this review, membrane compartments are classified as stable domains, transient compartments, or nanodomains where proteins aggregate. Interestingly, in most cases, the cortical cytoskeleton plays important roles. Recent studies of the membrane-cytoskeleton interface are providing new insights about membrane organization involving a scale-free self-similar fractal structure and cytoskeleton active processes coupled to membrane dynamics.