The blood-brain barrier (BBB) is the monocellular interface that divides the peripheral circulation from direct contact with the central nervous system (CNS). This interface consists of several parallel barriers that include most notably the capillary bed of the CNS and the choroid plexus. These barriers at one level create the dichotomy between the circulating factors of the immune system and the components of the CNS only to regulate interactions between the immune and central nervous systems at other levels. The BBB is thus an integral part of the neuroimmune axis. Here, we will consider four aspects of BBB-neuroimmune interactions: BBB disruption as mediated by LPS and cytokines, cytokine transport across the BBB, immune cell trafficking, and effects of lipopolysaccharide (LPS) on various functions of the BBB.