Needle stick injuries (NSIs) are prevalent in health care, with an estimated 600,000 to 800,000 occurring annually in the U.S., many of which go unreported. Health care professionals must be educated on the associated risks from pathogens like HIV, HBV, and HCV, and follow established protocols for exposure management, which may include post-exposure prophylaxis for HIV and vaccination for HBV. Effective response after an NSI involves immediate washing, reporting the incident, and evaluating the exposure to determine appropriate treatments.