Human cytomegalovirus (HCMV) has become a paradigm for viral immune evasion due to its unique multitude of immune-modulatory strategies. HCMV modulates the innate as well as adaptive immune response at every step of its life cycle. It dampens the induction of antiviral interferon-induced genes by several mechanisms. Further striking is the multitude of genes and strategies devoted to modulating and escaping the cellular immune response. Several genes are independently capable of inhibiting antigen presentation to cytolytic T cells by downregulating MHC class I. Recent data revealed an astounding variety of methods in triggering or inhibiting activatory and inhibitory receptors found on NK cells, NKT cells, T cells as well as auxiliary cells of the immune system. The multitude and complexity of these mechanisms is fascinating and continues to reveal novel insights into the host-pathogen interaction and novel cell biological and immunological concepts.