The evolution of understanding regarding key issues involved in immune reconstitution should allow movement from indirect supportive care of immuno-incompetence following HSCT to proactive measures designed to enhance reconstitution in this setting. Future clinical studies using lymphoid progenitors, thymoprotective agents and immunostimulatory cytokines are needed to test the clinical utility of these approaches and agents which have had promising results in preclinical models. Importantly, while solid pre-clinical supporting data exist for many agents and approaches, clinical application mustproceed carefully, with particular attention to issues that may depend critically on timing and dose. Allogeneic HSCT presents a challenging arena for the application of immune based therapies because of the need to respect the delicate balance between GvHD, GvT responses, rejection and reconstitution of specific immunity against pathogens. Armed with our current and rapidly evolving knowledge, it is hopes that the coming years will witness the evolutionary development of clinical practice in this arena.