Molecular components that activate and regulate the innate and adaptive immune systems have provided us with a plethora of novel targets for intervention to control the inflammatory response. This chapter focuses on those drug candidates thought to be most likely to succeed as therapies for acute inflammatory disease processes. It emphasizes therapies targeting pathogen-associated molecular pattern molecules (PAMPs), damage-associated molecular pathogens (DMPs), endothelial and epithelial barrier protection therapies, and regulators of cell apoptosis, autophagy, gene regulation, and survival. It highlights the attempts to limit systemic inflammation with selected agents designed to terminate persistent, nonresolving. We will also highlight attempts to limit systemic inflammation with selected agents designed to terminate persistent, nonresolving inflammation, and in some circumstances, provide immune reconstitution by bolstering host defenses against microbial toxins and virulence. Antivirulence therapies designed to disarm bacteria and render them harmless to the host is a future possibility.