Cell protrusions are outward extensions of the plasma membrane of individual cells that function in sensing the cell environment and in making initial, dynamic adhesions to extracellular matrix and other cells. Cell protrusions can be grouped into two major categories on the basis of morphology: localized, finger-like structures of highly defined shape and various lengths; or broad, irregular extensions of the plasma membrane. A key requirement of all cell protrusions is the need for a rigid cytoskeleton to support the localized extension of the plasma membrane. This is achieved either by a core unipolar bundle of actin microfilaments in finger-like protrusions, or by a combination of radial, rib-like, actin bundles integrated with a dendritic meshwork of microfilaments in the broad, lamellipodial protrusions. From studies of multiple cell types in vertebrates and invertebrates, fascin-1 has emerged as an actin-bundling protein of general importance for a diverse set of cell protrusions with functions in cell adhesion, cell interactions, and cell migration. This review discusses current knowledge of the molecular and cellular properties and functions of fascin, the roles of fascin-based protrusions in the cardiovascular system in health and disease, and areas of future interest.