Human recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) is traditionally used as supportive care for patients undergoing cytotoxic chemotherapy or haematopoietic cell progenitor mobilisation. Emerging evidence suggests rhuGM-CSF, through activity on monocytes and dendritic cells, acts as a potent modulator of immune responses and has the ability to recruit inflammatory cells and cytokines to local and systemic sites of infection. The immunomodulatory effects of rhuGM-CSF suggest the potential to enhance innate and acquired immune responses against tumour-related antigens. Enhancement of innate antitumour immunity, especially in the context of minimal residual disease, is of central importance and presents the potential for meaningful contributions to long-term disease survival. This article discusses the immunomodulatory effects of rhuGM-CSF in the context of single-agent therapy in solid tumours, as well as combination therapy in lymphoma. In addition, dendritic cell modulation with rhuGM-CSF in haematopoietic progenitor grafts and rhuGM-CSF-transduced tumour vaccines will be discussed.