This study investigated the efficacy of isoflurane in Madagascar hissing cockroaches (Gromphadorhina portentosa). Cockroaches (n = 12) were placed in a 2-L anesthesia chamber with isoflurane initiated at 5% at 2 L/m. Movement of antennae, mandibles, and legs and righting reflex were assessed, with full induction achieved when all responses had ceased for 2 m. Cockroach movement became ataxic on average (±SD) 3.5 ± 0.9 m after isoflurane treatment, and induction occurred on average 18.7 ± 4.4 m after treatment. Loss of righting reflex was the most consistent indication of full induction. Cockroaches fully recovered on average 16.2 ± 5.6 m after removal of isoflurane inhalant. Induction was uneventful, and no mortality or obvious morbidity was observed in treated cockroaches up to 30 d posttreatment. The authors conclude that the use of inhalant isoflurane is both safe and effective for anesthesia of Madagascar hissing cockroaches.