Severe damage to the central nervous system, i.e. beheading, head bashing, etc. Depends on your mythos, though. Are they merely walking autonomic systems or do they have some level of consciousness? What are the mechanisms that make them run? Biological or spiritual? In one story I read, spirits possessed cadavers and the center of their possession was the heart so you had to destroy the heart. If it's viral than any significant damage to the physical structure should be sufficient.