Kidney transplantation is the best possible treatment for many patients with end-stage renal failure, but progressive dysfunction and eventual allograft loss with return to dialysis is associated with increased mortality and morbidity. Immune injury from acute or chronic rejection and non-immune causes, such as nephrotoxicity from calcineurin inhibitors, ischaemia-reperfusion injury, recurrent glomerular disease, and allograft BK viral infection, are potential threats. Serial monitoring of renal function enables early recognition of chronic allograft dysfunction, and investigations such as therapeutic drug concentrations, urinalysis, imaging, and a diagnostic biopsy should be undertaken before irreversible nephron loss has occurred. Specific interventions targeting the pathophysiological cause of dysfunction include strengthening of immunosuppression for chronic rejection, or calcineurin inhibitor minimisation, substitution, or elimination if nephrotoxicity dominates. Recommended proactive preventive measures are control of hypertension, proteinuria, dyslipidaemia, diabetes, smoking, and other comorbidities. Strategies to maintain transplant function and improve long-term graft survival are important goals of translational research.