Within the past two decades, feline injection-site sarcomas have been recognized as a group of invasive tumors that represent a major treatment challenge in veterinary medicine. They were first linked to vaccine administration in the early 1990s, following a sharp increase in the number of killed rabies virus vaccinations administered to cats and a corresponding increase in the number of sarcomas diagnosed by veterinary pathologists. Though the exact etiopathogenesis remains partially uncharacterized, an aberrant inflammatory response is most likely at the root of the problem. Treatment is difficult due to the locally invasive properties of soft tissue sarcomas, making surgical excision challenging at best. Recommendations for reduced vaccine administration and standardized sites for injection have been made to decrease incidence and mortality associated with these lesions.