Previous studies have built up evidence that an unstable self-esteem is associated with vulnerability to depression and that it outperforms level of self-esteem as a predictor for symptoms of depression. However, most of these studies have used student samples exclusively to investigate the role of self-esteem instability in depression vulnerability. Our present study used samples of currently depressed inpatients, formerly depressed individuals, and never-depressed controls to investigate the relationship between self-esteem instability and depression. In addition, we examined the predictive validity of self-esteem instability in predicting future depressive symptoms. The results indicate that self-esteem instability is associated with depression and vulnerability to depression. Furthermore, self-esteem instability interacted with perceived stress variability and depressed mood variability in predicting future depressive symptomatology at six months follow-up. These results are in line with the diathesis-stress model and support the hypothesis that self-esteem instability might be more important than level of self-esteem in predicting vulnerability to depression.