The neutrophilic granulocyte (neutrophil) is the most important cellular component of the innate immune system. A total absence of neutrophils or a significant decrease in their number leads to severe immunodeficiency. A mature neutrophil, released from the bone marrow, should be able to migrate from the blood towards the tissues, following a chemotactic gradient to a pathogen. In order to be neutralized, this pathogen has to be recognized, phagocytosed, and destroyed by lytic enzymes contained in the neutrophil's granules and reactive oxygen species formed by the enzyme complex NADPH oxidase. Rare genetic defects leading to the loss of each one of these biological properties of the neutrophil have been described and are associated with immunodeficiency. This review provides a summary of the normal development and biological functions of neutrophils and describes the diseases caused by defects in neutrophil number and function.