Graft-versus-host disease (GVHD) is a risk of hematopoietic cell transplantation (HCT) in the clinical setting. The acute form of the disease is well managed, but the chronic form is more problematic. The canine HCT model, instrumental in establishing successful clinical HCT protocols, reproducibly recapitulates the clinical manifestations of GVHD. Thus, therapies for the prevention and treatment of GVHD in the canine model may be applicable to the clinic. Here, we present the methods necessary to establish both acute and chronic GVHD models in dogs.