Tight regulation of the actin cytoskeleton is critical for many cell functions, including various forms of cellular uptake. Clathrin-mediated endocytosis (CME) is one of the main methods of uptake in many cell types. An intact and properly regulated actin cytoskeleton is required for CME in Saccharomyces cerevisiae. Yeast CME requires the proper regulation of actin polymerization, filament cross-linking, and filament disassembly. Recent studies also point to a role for F-BAR and BAR-domain containing proteins in linking the processes of generating and sensing plasma membrane curvature with those regulating the actin cytoskeleton. Many of these same proteins are conserved in mammalian CME. However, until recently the requirement for actin in mammalian CME was less clear. Several recent studies in mammalian cells provide new support for an actin requirement in the invagination and late stages of CME. This review focuses on the regulation of the actin cytoskeleton during CME in yeast and the emerging evidence for a role for actin during mammalian CME.