The nine human herpesviruses have coevolved with the immune system of their host that controls them in asymptomatic persistent infection often for decades. Primary immunodeficiencies due to individual gene mutations suggest that natural killer (NK) cells are an important component of this immune control. In this chapter, I discuss how different NK cell subsets expand in response to distinct human herpesvirus infections. Moreover, the different functional abilities of the respective NK cell subsets point towards different requirements in immunological effector functions for the immune control of these herpesviruses. The respective studies provide us also with insights into how distinct human NK cell subsets can be expanded to use their functions for therapeutic interventions against uncontrolled human herpesvirus infection and treatments in tumor patients.