Endocytosis is a shared process by which molecules, proteins, lipids, and liquids are sorted inside the cell via formation of intermediate vesicles. Vesicle formation occurs at the plasma membrane, where ligand receptors, binding proteins, and structural proteins are localized. After their internalization, the vesicles containing protein receptors or soluble molecules undergo a round of recycling, eventually leading to the fusion of the vesicle with an intracellular organelle. Such a process is an essential hallmark in all cell types—it regulates major cellular functions such as antigen presentation, intracellular signaling cascades, cell polarity, and synaptic transmission. Moreover, it is required to remove aged and dead cells from the body and is part of the defense against microbes. Given its importance, it is not surprising that even subtle perturbations affecting the endocytic machinery often impair cell function and cause several pathological conditions, such as cancer, and neurological and storage diseases. Finally, endocytosis represents an important cellular route for targeted drug-delivery in many diseases.