Food is essential to life, hence #food #safety is a basic human right. Billons of people in the world are at risk of unsafe food. Many millions become sick while hundreds of thousand die yearly. The food chain starts from farm to fork/plate while challenges include microbial, chemical, personal and environmental hygiene. Historically, documented human tragedies and economic disasters due to consuming contaminated food occurred as a result of intentional or unintentional personal conduct and governmental failure to safeguard food quality and safety. While earlier incidents were mainly chemical contaminants, more recent outbreaks have been due to microbial agents. The Disability Adjusted Life Years (DALYs) attributed to these agents are most devastating to children younger than 5 years of age, the elderly and the sick. To ensure food safety and to prevent unnecessary foodborne illnesses, rapid and accurate detection of pathogenic agents is essential. Culture-based tests are being substituted by faster and sensitive culture independent diagnostics including antigen-based assays and polymerase chain reaction (PCR) panels. Innovative technology such as Nuclear Magnetic Resonance (NMR) coupled with nanoparticles can detect multiple target microbial pathogens' DNA or proteins using nucleic acids, antibodies and other biomarkers assays analysis. The food producers, distributors, handlers and vendors bear primary responsibility while consumers must remain vigilant and literate. Government agencies must enforce food safety laws to safeguard public and individual health. Medical providers must remain passionate to prevent foodborne illnesses and may consider treating diseases with safe diet therapy under proper medical supervision. The intimate collaboration between all the stakeholders will ultimately ensure food safety in the 21st century.