Neutrophils are endowed with a plethora of toxic molecules that are mobilized in immune responses. These cells evolved to fight infections, but when deployed at the wrong time and in the wrong place, they cause damage to the host. Here, we review the generalities of these cells as well as the difficulties encountered when trying to unravel them mechanistically. We then focus on how neutrophils develop and their function in infection. We center our attention on human neutrophils and what we learn from clinical immunodeficiencies. Finally, we use autoimmune disease to illustrate the harmful potential of dysregulated neutrophil responses.