Lactoferrin, an iron-binding glycoprotein, can be regarded as a cell-secreted mediator that bridges innate and adaptive immune function by regulating target cell response. It is a major pleiotropic mediator that directly assists in the development of T-helper cell polarization. The aim of this minireview is to provide a summary of the most recent work presented at the Lactoferrin Minisymposium at the University of Texas, Health Science Center at Houston, Texas, USA, regarding role of lactoferrin in maintaining immune homeostasis. The data presented here lay emphasis on the significance of lactoferrin in the resolution or progression of the immune responses, thus giving lactoferrin bookend properties in controlling the initial reactions to infectious assault, trauma, and injury. These findings may be critically important in the development of therapeutically relevant protocols.