Several studies have shown that minocycline, a semisynthetic, second-generation tetracycline derivative, is neuroprotective in animal models of central nervous system trauma and several neurodegenerative diseases. Common to all these reports are the beneficial effects of minocycline in reducing neural inflammation and preventing cell death. Here, the authors review the proposed mechanisms of action of minocycline and suggest that minocycline may inhibit several aspects of the inflammatory response and prevent cell death through the inhibition of the p38 mitogen-activated protein kinase pathway, an important regulator of immune cell function and cell death.