A detailed understanding of asymptomatic chronic viral infections is critical to analyse their pathogenesis, assess the severity and burden of disease and, where required, optimize public health control measures. Recent studies on herpesviruses showed that the host–virus interactions are modulated by co-infections, emphasizing the relevance of co-infections in determining the clinical expression (from asymptomatic to symptomatic infections) and the severity of herpesvirus-associated diseases (either neoplastic or infectious diseases). To demonstrate causality between viruses (virome) and diseases, Koch's postulates should be adapted adding new knowledge on host–microbe relationship and microbial interactions. In the present review we aim to provide an update on asymptomatic chronic infections and criteria for causality and on the virological, immunological and host–virus interactions in asymptomatic chronic infections in human hosts, focusing on herpetic infections.