Black shank disease, caused by the fungus Phytophthora parasitica var. nicotianae, is a major annual threat to all types of tobacco worldwide. Thus far, the main approaches to control this disease are the creation of resistant tobacco varieties and application of fungicide treatments. Some fungicides are reported to have negative effects on the environment. The goal of this work was to test the antifungal activity of several natural products that are synthesized by tobacco and other Nicotiana species, and secreted to the leaf surface. We hypothesized that phylloplanin, cis-abienol, labdene-diol and sclareol can suppress race zero and race one-caused disease in Burley tobaccos KY14 and KY14xL8. We developed methods for leaf surface extraction, spore preparation and soil application of working concentrations of the natural compounds tested. Experiments were performed on the five to eight week-old seedlings, in triplicates. cis-Abienol showed high inhibitory properties toward the disease. Race zero infection was completely subdued in KY14, and race one infection was reduced by 80% and 70% in KY14 and KY14xL8, and delayed by six to ten days. Sclareol was very effective in inhibiting race zero-caused disease in both tobacco lines. KY14xL8 race one infection was inhibited by sclareol while in KY14 it was reduced by 85% and delayed by six days. Labdene-diol reduced the disease by half in eight week-old KY14 plants. Tobacco phylloplanin reduced plant infection by both races by 50% to 60% and delayed the disease by six to ten days. We consider sclareol to be the best candidate for future studies due to its antifungal properties and availability. Despite the good antifungal activity of cis-Abienol, it is not feasible for a large scale soil application due to the production efforts.