In recent decades, continuous improvements in immunosuppressive therapy have led to a significant increase in kidney allograft survival. Despite innovative developments and improvements in immunosuppression, chronic allograft injury and late graft loss still remain major causes of morbidity and mortality. In clinical practice, long-term immunosuppression is adapted and fine-tuned according to drug levels, kidney function, and biopsy results. As an invasive procedure, indication biopsy still represents an indispensible diagnostic gold standard. However, in an effort to further improve outcomes on the basis of individualized treatment, there is an urgent need for noninvasive assays, as well as biomarkers, to more accurately monitor allogeneic responses and predict the risk of acute and chronic allograft rejection. This article discusses strategies for immune monitoring of T-cell responsiveness and humoral alloreactivity. Furthermore, new microarray and gene profiling data are highlighted, which may identify hyporesponsive transplant recipients who could benefit from a reduction or even withdrawal of immunosuppression. Finally, supplementary transplant risk assessment markers, such as soluble CD30 and urinary effector molecule analysis, are discussed as promising new tools. Recent developments and improvements in test principles to monitor and predict allograft immunity are encouraging and may herald the transition of present empiric immunosuppression to individualized immunosuppressive treatment. Nonetheless, before implementation of immune monitoring in routine clinical practice, there is still a need for prospective trials designed to clarify the actual diagnostic potential of individual test systems in a therapeutic context.