Man's first attempt to immunize susceptibles against smallpox infection was by variolation, a practice which could be traced back several thousand years. The attempt obviously failed to control the disease until Jenner discovered the effectiveness of cowpox vaccine during the late 18th century. However, it took an additional 180 years until the current smallpox vaccine--a modification of Jenner's vaccine--became fully effective, in terms of quality and usage during the global smallpox eradication campaign. The campaign appears to be on the threshold of success, which could well mean extinction of one of the most dangerous pathogens from the natural environment. If this is verified, we may say farewell to routine smallpox vaccination. The paper discusses different measures taken to ensure the quality and the use of smallpox vaccine in the best possible manner during the eradication campaign and, on its completion, the fate of smallpox vaccination.