Of all sites in the body, the lung is perhaps challenged by the greatest onslaught of microbial pathogens, many of which would cause lethal infections if unopposed. The immune response to respiratory infection must, therefore, be rapid and efficient. However, the respiratory tract is a fragile tissue with architecture that is finely designed for gas exchange, so that the price of excessive or inappropriate inflammatory responses may itself be very high. The first line of defence comes from barriers such as mucus and cilia, followed by a battery of mediators that constitute the innate response. These include lactoferrin, lysozyme, collectins and defensins. Activation of these molecules can lead directly to lysis of pathogens, or to destruction through opsonisation or the recruitment of inflammatory cells. The adaptive immune response includes the production of neutralising antibodies and the responses of T lymphocytes. Different populations of T lymphocytes may dramatically alter the balance between clearance of the pathogen and induction of tissue damage depending on the cytokines they secrete.