In avian species, adaptive immunity involves both humoral and cell-mediated immune (CMI) responses. Although humoral or antibody-mediated immune responses are particularly effective against extracellular antigens, CMI responses are specialized in the elimination of intracellular antigens; the latter include those that have entered cells via the endocytic pathway (exogenous antigens; e.g., phagocytosed bacteria) or were produced within the cell such as viral proteins and proteins resulting from neoplastic transformation of the cell (endogenous antigens). CMI responses, like most humoral immune responses, are tightly regulated and require "help" from T helper cells, specifically the type 1 T helper cells (Th1, hence, the name Th1 responses). Th1 cells are characterized by their production of cytokines such as interferon-γ (IFN-γ), tumor-necrosis factor-α (TNF-α), and interleukin-2 that drive CMI responses. The functional effectors of CMI responses are various immune cells including cytotoxic lymphocytes (cytotoxic T cells and natural killer cells) and macrophages. Cytotoxic lymphocytes and macrophages are specialized in the elimination of endogenous and exogenous antigens, respectively. In the past decade, substantial progress has been made in defining the role and regulation of avian CMI responses. Other advances have addressed strategies that strengthen this arm of adaptive immunity to optimize defense as well as protection against neoplastic diseases and nonneoplastic diseases caused by intracellular pathogens.