Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. This phenomenon inspired the development of numerous rudimentary cancer immunotherapies, with a history spanning thousands of years. Coley took advantage of this natural phenomenon, developing a killed bacterial vaccine for cancer in the late 1800s. He observed that inducing a fever was crucial for tumour regression. Unfortunately, at the present time little credence is given to the febrile response in fighting infections-no less cancer. Rapidly growing tumours contain large numbers of leucocytes. These cells play a part in both defence and repair; however, reparative functions can also support tumour growth. Intratumoural infections may reactivate defensive functions, causing tumour regression. Can it be a coincidence that this method of immunotherapy has been "rediscovered" repeatedly throughout the centuries? Clearly, Coley's approach to cancer treatment has a place in the past, present, and future. It offers a rare opportunity for the development of a broadly applicable, relatively inexpensive, yet effective treatment for cancer. Even in cases beyond the reach of conventional therapy, there is hope.