Chronic granulomatous disease is a rare and potentially fatal disorder of neutrophil function. Beyond current medical management and hematopoietic stem cell transplantation, new methods of gene therapy that use lentiviral vectors or gene editing might extend curative therapies to patients who lack a suitable transplantation donor while eliminating the risk of graft-versus-host disease. Furthermore, new therapies focused on altering the biology of phagolysosomes might offer novel targeted treatments for inflammatory complications in patients with chronic granulomatous disease.