The need for federally approved chemotherapeutants for use in domestic shrimp culture in the USA is acute. A summary of toxicity testing of 12 antimicrobials against penaeid shrimp larvae is presented. In addition, the toxicity data are examined in concert with previously reported data on minimum inhibitory concentrations to establish a therapeutic index (a measure of margin of safety) for each compound tested. The 11 prospective antimicrobials were compared with the reference compound, chloramphenicol. The antimicrobials tested were enrofloxacin, erythromycin, florfenicol, oxytetracycline, paromomycin, four experimental fluoroquinolines (PD124816, PD127391, PD131628, PD132133), Romet-30®, and Sarafin®. The top six compounds (in their relative order of safety, from the safest to the least safe) were PD127391, oxytetracycline, chloramphenicol, enrofloxacin, florfenicol, and Romet-30.