The potential relationship between systemic retinoids used in dermatology and affective disorders is controversial. Acitretin, which is widely used in the treatment of psoriasis is part of this controversy secondary to its chemical relation to isotretinoin, a drug which has been associated with a large number of anecdotal case reports of depression and suicidal ideation. Moreover, an FDA package insert precaution regarding acitretin's association with depression and suicide has elevated the level of concern for patient safety. The objective of this article is to review the evidence in the literature regarding acitretin's association with affective disorders. After 12 years of worldwide use only two cases involving acitretin have been reported in the literature. In addition, despite many anecdotal cases involving isotretinoin, there have been no clinical studies that have proven a causal relationship between isotretinoin and depression or suicidal ideation. For acitretin there have been no systematic clinical studies that examine such a relationship. Moreover, it is notable that the FDA precaution regarding depression and suicide on the package insert of acitretin predates the publication of the aforementioned two cases. This suggests that a relationship between acitretin and affective disorders is a class labeling rather than a scientifically proven association.