Clathrin-mediated endocytosis (CME) involves the timely coordination of plasma membrane deformation, clathrin coat assembly, and cargo inclusion. CME culminates with vesicle release through membrane scission, followed by internalization and uncoating en route to the endosome. The biochemical and biophysical requirements of CME are supplied by a broad number of regulators, many of which bind actin and/or modify actin dynamics. The multidomain structure of these regulators enables their integration into signal-based cellular programs. The architecture and dynamic nature of the actin cytoskeleton establish its influence on distinct aspects of CME, ranging from membrane compartmentalization and acquisition of membrane curvature to coated pit invagination and vesicle movement. However, in mammalian cells, the regulation of CME by the actin cytoskeleton may be facultative, as CME still occurs, in certain cellular contexts, in the absence of actin polymerization. This chapter addresses the complexity of CME regulation by actin and expands on the role of membrane compartmentalization on the spatial organization of clathrin-coated pits and on the multiplicity of differently structured regulators of actin dynamics at the coated pit.