This chapter discusses the roles of anticonvulsants and baclofen in trigeminal neuralgia. The anticonvulsants constitute the major drug therapy for trigeminal neuralgia (TN). An emerging body of RCT evidence supports first-line TN treatment with lamotrigine. Case series data for TN patients with multiple sclerosis found gabapentin and topiramate particularly useful. Baclofen, a gamma-aminobutyric acid (GABA) agonist usually used as an antispasticity agent, is an effective, though second-line, therapy for TN. Animal models of TN suggest that baclofen mediates pain relief via a mechanism that differs from that of carbamazepine. This is clinically relevant, because the complementary pain relief mechanisms of the two drugs may be responsible for the observation that pain relief is improved with dual therapy (i.e. baclofen plus carbamazepine). Although there is promise for baclofen's use in TN, the overall level of evidence is insufficient to recommend its first-line use in the ED setting.