Streptococcal disease is the cause of severe economic losses of farm-raised fish, especially in tilapia aquaculture. The causative bacteria are S. iniae and S. agalactiae, both of which are ubiquitous pathogens that infect all sizes of fish and for which no effective methods of control are available. These pathogens are reported to cause death rates of 30 to 50 percent in aquaculture operations. The disease is characterized by erratic swimming and behavior, missing or cloudy eyes, deformities and rapid death. The pathogens are highly infectious to brain tissues. Vaccination is the best method to prevent disease and offers the safest alternative to using antibiotics and chemicals that can contaminate food and the environment. However, no effective vaccines that prevent this disease were available for farm-raised fish. Fish vaccine development is more scientifically challenging than those developed for terrestrial vertebrates. To mitigate streptococcal disease in farmed food fish, the Agricultural Research Service’s (ARS) vaccine team developed two modified killed vaccines that consisted of formalinkilled cells and molecular fractioned extracellular products from S. iniae and S. agalactiae. The innovative combination of killed cells and extracellular product was demonstrated to provide safe and efficacious immune protection against streptococcal disease, in a manner superior to a vaccine that consisted of killed cells only. This type of cellular vaccine is the standard for the majority of fish vaccines today. The technology transfer mechanisms used were trust fund cooperative agreements, Cooperative Research and Development Agreements, patents, material agreements, and licensing. PerOs/Benchmark Biolabs received master vaccine cultures by material transfer agreement in 2008, and a license is pending. The company has estimated sales of 50 million vaccine doses at a customer cost of $1.9 million in 2009, with an increase in fish value of $10- 12 million annually. The potential economic benefit of these vaccines approaches $50 million annually worldwide.