Cell migration is an extremely complex but also a carefully orchestrated process. It involves the constant reconstruction of the cell shape, in order to adapt to an ever-changing plethora of external and internal stimuli. Time lapse movies of migrating cells often demonstrate a vigorous ruffling activity of the plasma membrane at the cell periphery, specifically at the forefront of the cells. From the film pictures, the motor underlying these activities might seem to be the flow of membranes and the “lipid flow model” for cell migration got a lot of attention during the eighties. The model stated that cell migration is primarily driven by a flow of lipid vesicles from the rear end to the leading end of the cells and it also stated an intimate relation between cell migration and the endocytic cycle. However, this model turned out to be, if not entirely wrong, at least incomplete, since it failed to take into account the activity of the cytoskeleton. We have barely started to recognise the mechanisms underlying the communication between the machinery for membrane dynamics and the regulators of cytoarchitecture. However, it is my sincere hope that this book will help to convince the reader that numerous vital cellular processes occur at the interface between lipid bilayers and proteins.