Gemcitabine has been used as a chemotherapeutic to treat solid cancers for more than 20 years. Whilst its use as chemotherapy has been declining due to the development of more potent chemotherapeutic combinations further studies of gemcitabine have identified varied immune modulatory effects on both tumour cells and leukocyte subsets. Despite these observations’ gemcitabine has rarely been used clinically on the basis of its immune modulatory properties. The recent successes of immunotherapy using checkpoint inhibition are not yet realised for many solid tumours, particularly those to which gemcitabine has proven efficacious. Novel combination immunotherapy involving gemcitabine, checkpoint inhibition and additional immune modulation has the potential to increase the efficacy of checkpoint inhibition whilst expanding the number of tumours susceptible to anti-tumour immunity. This commentary discusses gemcitabine’s immune modulatory properties and its potential role in combination immunotherapy.