Objective: Through a holistic health lens, the current study examines the effects of weight-related issues and stress on suicidality while controlling for depressive symptoms in college students. Participants: In total, 872 undergraduate and graduate students at DePaul University completed the American College Health Association-National College Health Assessment II Web-based survey in Spring 2010. Methods: Measures of suicidality, depression, weight-related issues, and life stressors were assessed, along with gender differences. Results: Females reported experiencing more weight loss attempts and total stressors than males. Weight-related issues and stress both significantly predicted depressive symptoms in a path analysis; depressive symptoms, in turn, significantly predicted suicidality. Gender differences were found; depressive symptoms mediate the relation between stress and suicidal behavior for females but not for males. Implications: This investigation furthers previous research on suicidality in college students and suggests that all-inclusive interventions that address weight-related issues and stress may help reduce depressive symptoms, which then may reduce suicidal behavior.