Virus-specific immune responses have a major impact on the outcome of the infection. Viral agents that are characterized by latency, such as herpesviruses and polyomaviruses, require a continuous immune control to reduce the extent of viral reactivation, as viral clearance cannot be accomplished, independently from the anti-viral treatment. In transplant patients, morbidity and mortality related to viral infections are significantly increased. In fact, the key steps of activation of T-cells are major target for anti-rejection immunosuppressive therapy and anti-viral immune response may be altered when infected cells and cellular effectors of immune response coexist in a transplanted organ. The role of cellular immune response in controlling viral replication and the main methods employed for its evaluation will be discussed. In particular, the main features, including both advantages and limitations, of available assays, including intracellular cytokine staining, major histocompatibility complex- multimer-based assays, Elispot assay, and Quanti FERON test, will be described. The potential applications of these assays in the transplant context will be discussed, particularly in relation to cytomegalovirus and polyomavirus BK infection. The relevance of introducing viro-immunological monitoring, beside virological monitoring, in order to identify the risk profile for viral infections in the transplant patients will allows for define a patient-tailored clinical management, particular in terms of modulation of immunosuppressive therapy and anti-viral administration. Virus-specific immune responses have a major impact on the outcome of the infection. Viral agents that are characterized by latency, such as herpesviruses and polyomaviruses, require a continuous immune control to reduce the extent of viral reactivation, as viral clearance can not be accomplished, independently from the anti-viral treatment. In transplant patients, morbidity and mortality related to viral infections are significantly increased. In fact, the key steps of activation of T-cells are major target for anti-rejection immunosuppressive therapy and anti-viral immune response may be altered when infected cells and cellular effectors of immune response coexist in a transplanted organ. The role of cellular immune response in controlling viral replication and the main methods employed for its evaluation will be discussed. and limitations, of available assays, including intracellular cytokine staining, major histocompatibili ty complex-multimer-based assays, Elispot assay, and Quanti FERON test, will be described. The relevance applications introducing these assays in the transplant context will be discussed, particularly in relation to cytomegalovirus and polyomavirus BK infection. The relevance of introducing viro- immunological monitoring, beside virological monitoring, in order to identify the risk profile for viral infections in the transplant patients will allow for define a patient-tailored clinical management, particular in terms of modulation of immunosuppressive therapy and anti-viral administration.