The plasma membrane of eukaryotic cells is primarily heterogeneous, featuring a wide variety of distinct subdomains that differ in lipid composition and biophysical properties. Some of these proteo-lipidic subdomains organize plasma membrane invaginations that have long been known to play a major role in the cellular uptake of cargo through a process known as endocytosis. Over the years, there has been an increased focus on understanding the basis for this heterogeneity and the physiological relevance of these different endocytic pathways. Among these different membrane domains, clathrin-coated pits (CCP) and caveolae are the most readily recognizable features when visualized through electron microscopy due to the presence of a distinct coat.