We analyzed ethnobotanical data on Kansas plants to evaluate differences among families for medicinal uses by Native Americans. We compared three different statistical methods used in previous ethnobotanical studies for use in our Native Medicinal Plant Research Program, which seeks to determine which plant families are more likely to contain species with medicinal compounds. The three approaches were linear regression, binomial approach, and Bayesian analysis. All were useful for determining medicinal plant use differences among plant families, although regression analysis was most useful for our purposes. Asteraceae and Fabaceae are abundant in the open sun environments of Great Plains grasslands and contain high numbers of medicinal plants. In contrast, although grasses (Poaceae) and sedges (Cyperaceae) also are species-rich and ecologically abundant, each is underrepresented as being used by Native Americans as medicine, which can be explained at least partially by their paucity of secondary compounds.