Personal and cultural forces leading to health care choices that deviate from conventional medicine have been minimally investigated. Success with treatment of illnesses is reliant on an adequate understanding of factors that influence attitudes and beliefs about medicine. The purpose of this study was to examine the relationship between attitudes toward complementary and alternative medicine (CAM) among college students as a function of American or Asian nationality, Familiarity/Exposure to CAM, and the personality construct of Openness to Experience. A web-based survey instrument was administered to 72 Asian international and 76 American college students at Indiana State University. No significant differences were found between attitudes of Asian students and American students. Within the total sample, positive attitudes toward CAM were found to be related to older age, more Familiarity/Exposure to CAM, and higher levels of Openness to Experience. After controlling for age, Familiarity/Exposure to CAM was found to be a significant predictor of positive attitudes in Asian students and Openness to Experience was found to be a significant predictor of positive attitudes in American students as initially hypothesized. Results are discussed in terms of their implications for health care professionals in addressing young adults‘ needs for effective and culturally sensitive treatment and a better understanding of predictors of CAM use.