Bacterial meningitis is one of the most difficult infectious diseases to treat because it affects the brain, which is separated from the rest of the systemic circulation by the blood-brain barrier (BBB), therefore all drugs targeting the brain must penetrate this barrier. Even if antibiotics can partially enter the brain, the issue of antibiotic-resistance is a constant threat. Moreover, when microglia, the immune sentinels of the brain, are activated by sensing the pathogens, a neuroinflammatory process is triggered and more immune cells from the systemic circulation invade the brain to eradicate the infection. As a result, the infiltrating immune cells break the endothelium of the BBB, and a defensive process turns out to be severely dangerous for the brain. Therefore, we need novel approaches besides antibiotics to fight infections, and we need them now. The strategy to block bacterial interactions with neurons can prevent neuronal death, pathological hallmark of all those neurological sequelae occurring even when the infection is successfully fought. At the same time, we also need to enhance the capacity of microglia of the brain to fight infections without the recruitment into the brain of other cells. Microglial cells can recognize the pathogens by sensing specific proteins either released or exposed on the outer surface of the bacteria and initiate phagocytosis process to kill them. We want to identify these proteins and use as immunostimulants to enhance their phagocytic function, and at the same time suppress neuroinflammation to maintain BBB integrity. In addition, neurons can also act themselves as immune cells, by exploiting their protein-degradation machineries to eliminate intracellular bacteria. The fight against bacterial meningitis can be successful only by preventing bacteria to kill neurons, and by making the brain immune cells an efficient army to kill pathogens without damaging the host.