Prophylactic vaccination against human cancer provides a unique opportunity to prevent human suffering for individuals at risk for tumor development. Appropriate vaccines may pose slightly different requirements than vaccines intended for therapeutic use. Prophylactic vaccines will need to prevent tumors far into the future, emphasizing the need to establish solid tumor-specific immunologic memory. Another important issue associated with prophylactic cancer vaccines is the identification of appropriate populations for vaccination. Individuals at risk may include those exposed to oncogenic viruses, those with occupational exposure to tumor promoting agents, and individuals with a family history of cancer. This paper addresses the specific challenges posed to the exciting field of prophylactic cancer vaccine research.