L-glutamate is the major excitatory neurotransmitter in the brain and is responsible for normal brain function. However, high glutamate exposure triggers neuronal death, a process known as excitotoxicity. Excitotoxicity is associated with acute and chronic neurodegenerative diseases. Treating excitotoxicity using glutamate-receptor antagonists has not proven clinically viable, necessitating more sophisticated approaches. Rothstein and colleagues discovered that beta-lactam antibiotics protect neurons from excitotoxicity by increasing the number of glutamate transporters, which have a key role in clearing glutamate from the extracellular space. The design of compounds capable of modulating glutamate uptake represents a novel strategy for the treatment of neurodegenerative diseases.