Acute rejection episodes are an important risk factor for the functional deterioration of solid-organ transplants. With more intense immunosuppressive protocols, the rate of acute rejection episodes has significantly declined in the last decade, but long-term graft function and graft survival are challenged by increasing viral complications. In this article, recent data on the role of adenovirus, polyomavirus BK and JC, cytomegalovirus, human herpesvirus-6 and -7, and parvovirus B19 on the long-term outcome of kidney transplantation are reviewed. An update on the pathophysiology of smoldering viral replication, associated inflammatory damage, and the presumed indirect viral effects is provided, and the implications for diagnostic tests and antiviral intervention are discussed.