We give the first systematic investigation of the design space of worm defense system strategies. We accomplish this by providing a taxonomy of defense strategies by abstracting away implementation-dependent and approach-specific details and concentrating on the fundamental properties of each defense category. Our taxonomy and analysis reveals the key parameters for each strategy that determine its effectiveness. We provide a theoretical foundation for understanding how these parameters interact, as well as simulation-based analysis of how these strategies compare as worm defense systems. Finally, we offer recommendations based upon our taxonomy and analysis on which worm defense strategies are most likely to succeed. In particular, we show that a hybrid approach combining Proactive Protection and Reactive Antibody Defense is the most promising approach and can be effective even against the fastest worms such as hitlist worms. Thus, we are the first to demonstrate with theoretic and empirical models which defense strategies will work against the fastest worms such as hitlist worms.