The article estimates the number of foodborne illnesses, hospitalizations, and deaths caused by unspecified agents in the United States. Using data from surveys, hospital records, and death certificates, the authors estimate that 38.4 million episodes of domestically acquired foodborne gastroenteritis were caused by unspecified agents, resulting in 71,878 hospitalizations and 1,686 deaths. The study highlights the significant contribution of these unspecified agents to the total burden of foodborne diseases, which is often underestimated in previous estimates. The methods used to estimate these figures include combining data from various sources, applying probability distributions to account for uncertainty, and subtracting the number of illnesses caused by known pathogens. The article also discusses the limitations and challenges in estimating the impact of unspecified agents and suggests future improvements, such as validating estimates using additional data sources and identifying new agents linked to foodborne transmission.The article estimates the number of foodborne illnesses, hospitalizations, and deaths caused by unspecified agents in the United States. Using data from surveys, hospital records, and death certificates, the authors estimate that 38.4 million episodes of domestically acquired foodborne gastroenteritis were caused by unspecified agents, resulting in 71,878 hospitalizations and 1,686 deaths. The study highlights the significant contribution of these unspecified agents to the total burden of foodborne diseases, which is often underestimated in previous estimates. The methods used to estimate these figures include combining data from various sources, applying probability distributions to account for uncertainty, and subtracting the number of illnesses caused by known pathogens. The article also discusses the limitations and challenges in estimating the impact of unspecified agents and suggests future improvements, such as validating estimates using additional data sources and identifying new agents linked to foodborne transmission.