Production of cytokines by immune cells in response to stimuli and the binding of cytokines to specific receptors on target cells is a central feature of the immune response. The IL-12 cytokine family is particularly influential in determining the fate of T cells and is characterized by the sharing of cytokine and receptor subunits. A thorough understanding of the molecular interactions within this family will be a key to the development of therapeutic inhibitors or enhancers of IL-12 family function. While the current structural and molecular data for IL-12 family members is limited, there is ample information on the structurally related IL-6 cytokine family. This review will summarize the current structural and mutagenesis data within the IL-12 family and will attempt to utilize similarities between the IL-6 and IL-12 families to understand molecular interactions between IL-12 family subunits and with receptor components.