Numerous effector reactions are involved in antiviral immunity. The antibody and T-cell-mediated reactions are the best-understood processes of the adaptive immune response against influenza virus. One of the essential mechanisms of virus infection control is cell-mediated cytotoxicity, which can act in an antibody-dependent or -independent fashion and is provided by different effector cells. The most specialized killers are CD8 T cells, which recognize specific pathogen proteins that are exposed by MHC class I molecules on the surface of the virus-infected cell. The role of CD8 T cells in infection control and in affecting the pathological outcome of different types of infection has been demonstrated in numerous animal studies. Despite this, the role of this T-cell subset in controlling human influenza infection is not fully understood. Especially, knowledge about their induction and turnover in human influenza infection is limited, since there have been few studies of tissue-associated CD8 T cells in humans. In addition, the role of vaccine-induced CD8 T cells in humans is not clear. Differences in the development of CD8 T cells after influenza infection or immunizations should be explored in detail, in relation to the bioaccessibility of influenza antigens, site of application and distribution routes. All these criteria can dramatically influence the CD8 T-cell immune response. Areas covered. This review focuses on the basic aspects of CD8 T-cell immune response both in human influenza virus infection and after administration of inactivated or live attenuated vaccine. Some aspects of the accessibility, distribution and presentation of influenza antigens to CD8 T cells are described. This review also examines some mechanisms of CD8 T-cell responses that were discovered for other viral infections but could be translated into influenza virus research. Expert commentary. The role of CD8 T cells in influenza infection received much attention in fundamental and applied immunological studies. Most studies have used animal models, which only partially resemble human CD8 T-cell immunobiology. The gap between fundamental immunological and vaccinological understanding of the CD8 T-cell response upon natural influenza infection and vaccination has not yet been bridged. The CD8 T-cell response is an essential connection between innate and antibody-mediated responses, which are all-important for influenza control. We hypothesize that immunization with live influenza vaccine is the most straightforward artificial way to induce an efficient influenza-specific CD8 T-cell response.