Neutrophils are critical components of the innate immune response, and persistent neutropenia is associated with a marked susceptibility to infection. There are a number of inherited clinical syndromes in which neutropenia is a prominent feature. A study of these rare disorders has provided insight into the mechanisms regulating normal neutrophil homeostasis. Tremendous progress has been made at defining the genetic basis of these disorders. Herein, progress in understanding the genetic basis and molecular mechanisms of these disorders is discussed. We have focused our discussion on inherited disorders in which neutropenia is the sole or major hematopoietic defect.