Purpose: The purposes of this study were to identify factors affecting depression in college students and the corre-lation of depression with self-esteem and academic stress, and to identify differences among student self-esteem, academic stress, and general characteristics and the relation ship of these variables to depression. Methods: The study was done in April 2011 with 852 students in health-related majors (medicine, nursing science, and dental hygiene) of a medical college in Korea. A self-rating survey containing 10 items from the Rosenberg Self-esteem Scale, 20 items from the Self-rating Depression Scale, and 22 items on academic stress was used. Data were analyzed using descriptive statistics, t-tests, one0way ANOVA, and logistic regression. Results: Medical students` scores for self-esteem were significantly higher than dental hygiene students, but for academic stress scores, the result was the opposite. Logistic regression showed that self-esteem, academic stress, academic major and satisfaction with it (positive affect), and home income level (negative affect) significantly affected the level of depression. Conclusion: Designing and implementing realistic programs tailored to students` academic majors to enhance their self-esteem and implementing realistic programs tailored to students` academic majors to enhance their self-esteem and provide practical knowledge in dealing with academic stress will help these stu-dents obtain a healthier school life emotionally as well as academically.