We present the case of a 37-year-old Indigenous renal transplant patient who developed a severe varicella zoster virus (VZV) infection with graft dissemination, requiring explantation of the graft. The patient’s immunosuppression protocol included antithymocyte globulin induction, tacrolimus, mycophenolate and prednisolone. Following the transplant, delayed graft function was observed. A perinephric collection was found and evacuated on post operative day 8. Although a transient improvement in renal function was noted, during the second post operative week, a vesicular rash developed over the surgical incision and right flank without distinct dermatomal distribution. A Tzanck smear of vesicular fluid confirmed the VZV diagnosis. The patient experienced a reactivation of cytomegalovirus and developed symptomatic disseminated viraemia. An acute decrease in GCS was also observed and found to have been the result of VZV encephalitis. The patient was then shifted to ICU. Here, immunosuppressive agents were ceased, whilst intravenous antiviral therapy commenced. Following worsening pain over the transplant, the patient underwent surgical exploration of the site. The graft was found to be non-viable and subsequently explanted. Over the next four weeks, the patient underwent ten relook procedures and on day 40 post explantation, had a definitive wound closure and split thickness graft placed. Although immunosuppression prevents organ rejection and is important for a transplant’s long-term success, increased susceptibility to infection and implications on morbidity and mortality must be weighed. Striking a balance is important. However, in such cases, infection management must be prioritised to optimise patient well-being.