The immune system consists of a complex network of a large number of cell types and a cascade of soluble factors, all of which work in concert to induce protective responses against a continuous challenge from a wide range of pathogens. A properly functioning avian immune system is vital for protection against a number of pathogens and in inducing a strong immune response to vaccination. As is the case with other body systems, the immune system is vulnerable to different diseases. This chapter focuses on immune system tumors. Although some tumors can arise from non-infectious causes, the vast majority of the tumors of the avian immune system have a viral etiology, with Marek’s disease virus, avian leukosis virus and reticuloendotheliosis virus as the etiological agents. By inducing tumors of the different hematopoietic cell lineages, these viruses have a profound influence on the strength and intensity of immune responses.