Infection by several different pathogens triggers perpetual bouts of neutrophil recruitment and breach of the airway epithelium. In the airspace, neutrophils encounter persistent microbial biofilms and release neutrophil extracellular traps (NETs) that are ineffective and ultimately repurposed for the benefit of the microbial biofilms. Following continuous cycles of acute infection or once chronic infection is established, T lymphocytes are recruited and polarized to Th1, Th2 and/or Th17 cells. IL-17A and related cytokines, as well as IFN-γ play an important role in the excessive recruitment of neutrophils. The effector phase of ABPA, associated to A. fumigatus infections, is determined by Th2-mediated allergic responses, including eosinophilia, mucus production, and airway hyperresponsiveness. The relevance of other emerging pathogens in CF lung disease progression still remains to be fully elucidated. N, Neutrophils; Mφ, macrophages; D, dendritic cells; B, B cells.