The opportunistic gram-negative bacterium Pseudomonas aeruginosa is implicated in many chronic infections and is readily isolated from chronic wounds, medical devices, and the lungs of cystic fibrosis patients. P. aeruginosa is believed to persist in the host organism due to its capacity to form biofilms, which protect the aggregated, biopolymer-embedded bacteria from the detrimental actions of antibiotic treatments and host immunity. A key component in the protection against innate immunity is rhamnolipid, which is a quorum sensing (QS)-regulated virulence factor. QS is a cell-to-cell signaling mechanism used to coordinate expression of virulence and protection of aggregated biofilm cells. Rhamnolipids are known for their ability to cause hemolysis and have been shown to cause lysis of several cellular components of the human immune system, for example, macrophages and polymorphonuclear leukocytes (PMNs). In this chapter, the interplay between P. aeruginosa and the PMNs in chronic infections is discussed with focus on the role of rhamnolipids and extracellular DNA.