Synaptic plasticity defines the process by which synapses, the connections between neurons, can be modified in response to activity. Plasticity can be either positive or negative, with strengthening and weakening of synapses occurring with distinct patterns of activity (neuronal "experience"). These plastic changes can be transient (lasting seconds to minutes) or can persist for days to months. Long-lasting forms of synaptic plasticity are supported by the de novo synthesis of macromolecules. This process can be broadly divided into transcription of DNA into new messenger RNAs and translation of mRNAs into new proteins. A very useful experimental platform for studying these processes is the rodent ex vivo hippocampal slice preparation. Hippocampal slices can be utilized for pharmacological, biochemical, and electrophysiological experiments aimed at studying mechanisms upstream and downstream of the macromolecular synthesis underlying persistent synaptic plasticity.