The neuroprotective properties of tetracyclines have been clearly established in rodent models of acute and chronic neurodegeneration during the past few years. Recent findings have provided novel insights into the molecular and cellular mechanisms of protection of neurons and oligodendrocytes by tetracyclines. These advances have prompted several clinical trials with minocycline, the most effective tetracycline, which are still in their early phases. Thus, tetracyclines hold great promise as therapeutic agents for the treatment of human neurodegenerative diseases.