The impact of CMV infection and disease in solid organ transplant (SOT) recipients continues despite remarkable improvements in its prevention and management with antiviral drugs. Studies that have investigated the host immune response to CMV have paved way for the development of novel immune-based assays that are anticipated to complement the current antiviral-based strategies for CMV management after transplantation. In this article, we review the emerging data on the clinical application of innovative CMV-specific T-cell assays, including their role in risk-stratification, prognostication, prevention and treatment of CMV infection and disease in SOT recipients.