Pseudomonas aeruginosa uses a type III secretion system (T3SS) to directly inject four known effectors into host cells. ExoU is a potent cytotoxin with phospholipase A2 activity that causes rapid necrotic death in many cell types. The biological function of ExoY, an adenylate cyclase, remains incompletely defined. ExoS and ExoT are closely related bifunctional proteins with N-terminal GTPase activating protein (GAP) activity toward Rho family proteins and C-terminal ADP ribosylase (ADPRT) activity toward distinct and non-overlapping set of targets. While almost no strain encodes or secretes all four effectors, the commonly found combinations of ExoU/ExoT or ExoS/ExoT provides redundant and failsafe mechanisms to cause mucosal barrier injury, inhibit many arms of the innate immune response, and prevent wound repair.