Over the past few years, foodborne disease outbreaks linked to enteric pathogens present on cantaloupe and watermelon surfaces have raised concerns in the melon industry. This research evaluated the effectiveness of commercially available produce sanitizers against selected foodborne pathogens, both in cell suspensions and on the outer rind surface of melons. The sanitizers (65 and 200 ppm of chlorine, 5 and 35% hydrogen peroxide, 5 and 50 ppm of liquid chlorine dioxide, various hydrogen peroxide-acid combinations, 0.78 and 2.5% organic acids, and 300 ppm of quaternary ammonium) were tested against Escherichia coli O157:H7, Listeria monocytogenes, Salmonella, and non-O157 Shiga toxin-producing E. coli (O26, O45, O103, O111, O121, and O145). The cell suspension study revealed the ability of all tested sanitizers to reduce all selected pathogens by 0.6 to 9.6 log CFU/ml in vitro. In the melon study, significant differences in pathogen reduction were observed between sanitizers but not between melon types. The most effective sanitizers were quaternary ammonium and hydrogen peroxide-acid combinations, with 1.0- to 2.2-log CFU/g and 1.3- to 2.8-log CFU/g reductions, respectively, for all pathogens. The other sanitizers were less effective in killing the pathogens, with reductions ranging from 0.0 to 2.8 log CFU/g depending on pathogen and sanitizer. This study provides guidance to the melon industry on the best produce sanitizers for use in implementing a broad-spectrum pathogen intervention strategy.