Invasive crayfish (family Cambaridae) displace native crayfish species and alter aquatic habitat, community structure, and ecosystem function. We evaluated whether chemical control can be a reliable control agent for crayfish to ensure that shipments from fish hatcheries did not result in new infestations of invasive crayfish. A series of acute (≤1 h) toxicity tests were conducted to evaluate the toxicity of cypermethrin and pyrethrin to crayfish, freshwater mussels, and fish; chemical concentrations in test organisms; effectiveness of carbon-block filters to remove cypermethrin from test waters; and the cost of chemical control relative to extra handling of fish. Cypermethrin dosed at 75 μg/L for 15 min resulted in 100% mortality of adult white river crawfish Procambarus acutus and virile crayfish Faxonius virilis but did not cause >20% mortality in adult pondmussel Ligumia subrostrata, juvenile fatmucket Lampsilis siliquoidea, fingerling Bluegill Lepomis macrochirus, hybrid sunfish (Bluegill × Green Sunfish L. cyanellus), hybrid Striped Bass (White Bass Morone chrysops × Striped Bass M. saxatilis), yearling Paddlefish Polyodon spathula, or ready-to-eat Bluegill, hybrid sunfish, and Channel Catfish Ictalurus punctatus. Behavioral effects, such as loss of equilibrium or head shaking, were generally limited to 1 h postexposure. Mean concentrations of cypermethrin increased in fish fillets (4–26 μg/g) and whole fish (5–1,770 μg/g); therefore, regulations limiting harvest for up to 7 d following stocking may be required. A carbon-block filtration system was effective in reducing (<90%) cypermethrin concentrations and thus reducing potential effects to nontarget species in receiving waters. Extra handling of fish was more cost-effective for all fish tested except for Paddlefish, where the cost of chemical control was half that for extra handling. For all other fish tested, chemical control was 4–10 times more expensive than extra handling. Special use permits or chemical registration are needed before chemical control for crayfish could be routinely used at fish hatcheries.