The present invention provides, in certain aspects, devices and methods for plugging passageways and other open spaces in the body. In one embodiment, a plugging assembly comprises a first plug member and a second plug member, wherein the second plug member is configured to contact and move a portion of the first plug member in plugging a body passageway. These plug members may be formed with one or more of a variety of biocompatible materials including some that are naturally derived and some that are non-naturally derived. In another embodiment, such a plugging assembly is combined with a device that is suitable for delivering the assembly into a body passageway.