Feline vaccine-associated sarcomas have presented many challenges. Initially, the etiopathogenesis and biological behavior of these tumors had to be characterized, and strategies implemented to move tumors away from problematic sites. Next, diagnostic and treatment recommendations evolved as the biologic behavior of vaccine-associated sarcomas forced early and aggressive intervention. Current therapeutic strategies are expensive, at times debilitating, and frequently fail to effect tumor control. This review summarizes the known history, epidemiology, etiology, and clinical management of vaccine-associated sarcomas after a decade of work. The next challenges must be to find more practical and effective solutions, and to eliminate the cause of vaccine-associated sarcomas.