In this review we describe the potential roles of the actin cytoskeleton in receptor-mediated endocytosis in mammalian cells and summarize the efforts of recent years in establishing a relationship between these two cellular functions. With molecules such as dynamin, syndapin, HIP1R, Abp1, synaptojanin, N-WASP, intersectin, and cortactin a set of molecular links is now available and it is likely that their further characterization will reveal the basic principles of a functional interconnection between the membrane cytoskeleton and the vesicle-budding machinery. We will therefore discuss proteins involved in endocytic clathrin coat formation and accessory factors to control and regulate coated vesicle formation but we will also focus on actin cytoskeletal components such as the Arp2/3 complex, spectrin, profilin, and motor proteins involved in actin dynamics and organization. Additionally, we will discuss how phosphoinositides, such as PI(4,5)P2, small GTPases thought to control the actin cytoskeleton, such as Rho, Rac, and Cdc42, or membrane trafficking, such as Rab GTPases and ARF proteins, and different kinases may participate in the functional connection of actin and endocytosis. We will compare the concepts and different molecular mechanisms involved in mammalian cells with yeast as well as with specialized cells, such as epithelial cells and neurons, because different model organisms often offer complementary advantages for further studies in this thriving field of current cell biological research.