Although most bacterial infections of the skin prove to be minor in nature, a few such dermatologic entities are significant, to the point of even being fatal. Their course can be extremely rapid and can lead to dreadful complications. The mortality rate is usually up to 30% to 50% and depends upon the type of infection, underlying disease, and immune status. Patients suffering them usually need to be hospitalized, sometimes in intensive care or burn units. They should be treated systemically with appropriate antimicrobial therapy plus aggressive supportive care. The two life-threatening skin infections which are most commonly experienced are toxin-mediated staphylococcal and streptococcal disorders; one could overlap the other. Several other related entities will also be discussed.