The ability of neutrophils and other leucocyte members of the innate immune system to expel their DNA into the extracellular environment in a controlled manner in order to trap and kill pathogenic microorganisms lead to a paradigm shift in our understanding of host microbe interactions. Surprisingly, the neutrophil extracellular trap (NET) cast by neutrophils is very wide and extends to the entrapment of viruses as well as multicellular eukaryotic parasites. Not unexpectedly, it has emerged that pathogenic microorganisms can employ a wide array of strategies to avoid ensnarement, including expression of DNAse enzymes that destroy the lattice backbone of NETs. Alternatively, they may use molecular mimicry to avoid detection or trigger events leading to the expression of immune modulatory cytokines such as IL-10, which dampen the NETotic response of neutrophils. In addition, the host microenvironment may contribute to the innate immune response by the production of lectin-like molecules that bind to bacteria and promote their entrapment on NETs. An example of this is the production of surfactant protein D by the lung epithelium. In addition, pregnancy provides a different challenge, as the mother needs to mount an effective response against pathogens, without harming her unborn child. An examination of these decoy and host response mechanisms may open the path for new therapies to treat pathologies mediated by overt NETosis.