Allogeneic haemopoietic stem cell transplantation (HSCT) is a potentially curative option for a wide range of haematological diseases. Graft versus Host Disease (GVHD) is an inflammatory disorder in the recipient, which accounts for significant morbidity and mortality after allogeneic HSCT and directly limits the success of this procedure. Current treatment options for GVHD include intense immunosuppression, which in turn has associated side effects, an increased risk of infective complications, and a potential for increased relapse of haematological malignancy. A major benefit of allogeneic HSCT arises from reduced relapse rate of the underlying disease, which is believed to be due to the graft versus tumour or graft versus leukaemia (GVL) effect where donor immune cells recognize recipient tumour antigens. It is well established that GVL is linked to the occurrence of GVHD. Effective prophylaxis of GVHD while allowing some GVL effect is an important, yet currently elusive, therapeutic goal in HSCT. Strategies to prevent GVHD include T-cell depletion, immunosuppression, gut decontamination and appropriate donor selection. Cyclosporin (CsA) and/or methotrexate (MTX) have formed the basis of many GVHD prophylaxis strategies with no major advances on this gold standard for over twenty years. This review seeks to outline the most effective methods for the prevention of GVHD with a particular emphasis on large randomised trials. Evidence on standard regimens, appropriate dosing and emerging strategies for GVHD prophylaxis for both myeloablative and reduced intensity conditioning HSCT will be explored.