The pathogenesis of infectious diseases is regulated by a complex interplay between microbes and the immune system. To function well, the immune system is dependent on factors in both the internal and the external environment. Behavioural, social and cultural factors are all important. Increasing resistance to drugs and greater awareness of other side effects of antibiotics have led to greater recognition by doctors of the need to use alternative ways of treating and preventing infections, particularly by modulating the immune response. Important elements of the defence against various types of infectious agents are outlined. This is intended as a framework for understanding how infectious diseases can be dealt with by modulating the immune response instead of only attempting to kill the microbe. This is particularly important in patients with serious infections and in groups of patients specially predisposed to infections.