College campuses often host students who come from families where one or more parent has been affected by a bipolar or depressive disorder. The present study sought to determine whether these students face unique challenges in college, including increased adjustment difficulties as well as greater caregiving burden associated with their parents' illness. Participants (N?=?89) were undergraduate students at a large public university in the South (27 had a parent with bipolar disorder; 30 had a parent with major depressive disorder [MDD]; 32 had no parent history of a mood disorder). Semistructured interviews were used to assess student symptoms of mood disorders and mood disorder symptoms within their immediate family. Self-report measures were used to assess college adjustment and levels of caregiving burden faced by the students. We found that students with a family history of bipolar disorder and MDD had significantly greater difficulty adjusting to college. These difficulties persisted even after controlling for whether the student themselves had been affected by a mood disorder. The students of a parent with either bipolar disorder or MDD also reported significantly more burden associated with caring for their parents. College campus mental health professionals need to be aware that students with a parent with bipolar disorder or MDD face unique challenges adjusting to college that are only partially related to an increased risk for mood disorders.