In the natural environment, many bacterial secondary metabolites are likely to play roles in mediating interactions with other microorganisms. Recently, a marine Halobacillus salinus isolate was found to produce secondary metabolites capable of quenching quorum sensing controlled phenotypes in several Gram-negative reporter strains. The isolate was initially observed to inhibit Vibrio harveyi bioluminescence, a cell signaling regulated behavior, in co-cultivation experiments. Using bioassay-guided fractionation, two phenethylamide metabolites were identified as the active agents. The compounds additionally inhibited quorum sensing regulated violacein biosynthesis by Chromobacterium violaceum CV026 and green fluorescent protein production by Escherichia coli JB525. Bacterial growth was unaffected at concentrations below 200 μg/mL. To investigate how widespread the production of such compounds may be in the marine environment, 332 Gram-positive isolates from diverse habitats were tested for their ability to interfere with V. harveyi bioluminescence using similar co-cultivation methods. A total of 49 isolates inhibited bioluminescence without visible cell killing effects. Chemical extracts were generated from cultures of the active isolates, and 28 reproduced the desired activity. Of those 28, five extracts additionally inhibited violacein production by C. violaceum. Most of the active isolates belong to either the genus Bacillus or Halobacillus. These results suggest that Gram-positive marine bacteria may be worthy of further investigation for the discovery of quorum sensing antagonists.