The plasma membrane forms a barrier to protect the cell from the outside world. However, the cell surface is not a static impermeable barrier but a dynamic mosaic of distinct domains with unique properties and functions. Our work is aimed at understanding the formation, function, and dynamics of these surface domains at the molecular level. We have focussed on two specific plasma membrane domains: caveolae, small pits of the cell surface, and the T-tubule system, an extensive system of surface-connected tubules in muscle cells. I will describe the use of light and electron microscopic techniques, including real-time confocal microscopy in whole organisms, cryoelectron microsocopy, electron tomography, serial blockface scanning electron microscopy, and genetically-encoded electron microscopic tags, to gain a quantitative understanding of the formation and function of these specific plasma membrane domains.