The BioSense program was launched in 2003 with the aim of establishing a nationwide integrated public health surveillance system for early detection and assessment of potential bioterrorism-related illness. The program has matured over the years from an initial Centers for Disease Control and Prevention–centric program to one focused on building syndromic surveillance capacity at the state and local level. The uses of syndromic surveillance have also evolved from an early focus on alerts for bioterrorism-related illness to situational awareness and response, to various hazardous events and disease outbreaks. Future development of BioSense (now the National Syndromic Surveillance Program) includes, in the short term, a focus on data quality with an emphasis on stability, consistency, and reliability and, in the long term, increased capacity and innovation, new data sources and system functionality, and exploration of emerging technologies and analytics.