Risk factors for development of inhibitors (neutralizing antibodies) against treatment products used to stop or prevent bleeding in hemophilia patients include 3 major categories. The causative mutation in the gene for FVIII or FIX has been shown to be the most significant risk factor, as whether a gene product is produced or its structure determines how the immune system recognizes the infused protein. The treatment product itself, how much exposure has occurred, and conditions of that exposure provide the trigger for the immune response. Determinants within the immune system control the response through a multiplicity of genes producing a wide phenotypic variability. Interaction of these 3 components, illustrated by the overlapping circles of the Venn diagram, provides each person with hemophilia with a highly individualized risk of developing this complication of treatment at some point during his or her lifetime. Professional illustration by Ken Probst, Xavier Studio.