OBJECTIVE To examine symptom clusters in oncology patients; to determine if these symptom clusters might share a common biologic mechanism; and to describe potential biologic mechanisms that warrant investigation. METHODS Synthesis of the theoretical and research papers on symptom clusters. CONCLUSIONS Definitive conclusions about whether there is a biologic basis for the clustering of symptoms cannot be determined at this time. The animal model of sickness behavior holds promise as a potential biologic mechanism for clustering symptoms. CONCLUSIONS Until more definitive studies of symptom clusters are performed, clinicians need to monitor patients for the co-occurrence of multiple symptoms and develop appropriate management plans.