Monkeypox 2022 exhibits unprecedented human-to-human transmission and presents with different clinical features than those observed in prior outbreaks. Previously endemic only to West and Central Africa, the monkeypox virus spread rapidly world-wide following confirmation of a case in the United Kingdom on May 7, 2022 of an individual that had traveled to Nigeria. Detection of cases with no travel history confirms on-going community spread. Emergency Medical Services (EMS) professionals will likely encounter patients suspected or confirmed to have monkeypox, previously a rare disease and therefore unfamiliar to most clinicians. Consequently, it is critical for EMS medical directors to immediately implement policies and procedures for EMS teams – including emergency medical dispatchers – to identify potential monkeypox cases. These must include direction on actions EMS professionals should take to protect themselves and others from virus transmission. Monkeypox 2022 may manifest more subtly than it has historically. Presentations include a subclinical prodrome and less dramatic skin lesions – potentially limited to genital or anal body regions – which can be easily confused with dermatologic manifestations of common sexually transmitted infections (STIs). While most readily spread by close contact with infectious skin lesions on a patient, it is also transmissible from fomites, such as bed sheets. Additionally, droplet transmission can occur, and the virus can be spread by aerosolization under certain conditions. The long incubation period could have profound negative consequences on EMS staffing if clinicians are exposed to monkeypox. This report summarizes crucial information needed for EMS professionals to understand and manage the monkeypox 2022 outbreak. It presents an innovative Identify-Isolate-Inform (3I) Tool for use by EMS policymakers, educators, and clinicians on the frontlines who may encounter monkeypox patients. Patients are identified as potentially exposed or infected after an initial assessment of risk factors with associated signs and symptoms. Prehospital workers must immediately don personal protective equipment (PPE) and isolate infectious patients. Also, EMS professionals must report exposures to their agency infection control officer and alert health authorities for non-transported patients. Prehospital professionals play a crucial role in emerging and re-emerging infectious disease mitigation. The monkeypox 2022 3I Tool includes knowledge essential for all clinicians, plus specific information to guide critical actions in the prehospital environment.