An infectious disease, as the name implies, is caused by pathogenic microorganisms such as bacteria, viruses, parasites, and fungi, and it spreads from one person to another through various ways, directly or indirectly. Most, but not all, of such diseases present to the ED with fever. Septic shock, respiratory failure, or central nervous system involvement may occur following an infection and threaten life. Such a situation presenting with tachycardia, reduced BP, tachypnoea, or depressed GCS requires immediate assessment and resuscitation. Following the principles of ABCDE, promptly carry out airway protection, oxygenation, and IV access with collection of blood samples for investigations, and fluid resuscitation. The aetiology of fever may be wide ranging, but a careful history and a detailed physical examination should help in determining the cause in majority of cases presenting to the ED. In addition to this, the initial investigations may help further in establishing the diagnosis. In elderly patients, the source of such infections may be the respiratory system, the genitourinary system or the involvement of the soft tissues, and they are often serious. In the otherwise healthy younger patient, one must keep in mind the other systems such as the central nervous system, as well as abdominal and soft tissue infections. Patients may often present in septic shock. Even if the cause of a fever may not be evident at the outset, the best ‘guestimate’ often helps in determining which antibiotics to start with, which should be given as soon as the culture samples have been collected. One must make every effort to collect appropriate samples of body fluids (blood, urine, stool, sputum, etc.) to find the source of infection so that targeted antimicrobial therapy may be started if the empirical treatment has not worked. A discussion with the on-call microbiologist to properly direct the empirical antibiotic therapy is often most rewarding. A patient with an infectious disease may put others at risk as well, resulting in devastating effects, particularly in hospitals.