Established and emerging tickborne infections are significant causes of human illness in the southern United States. Rocky Mountain spotted fever, human monocytic ehrlichiosis, human ewingii ehrlichiosis and tularemia are known pathogens in this geographic distribution. Rickettsia parkeri and novel ehrlichioses are more recently described tickborne infections reviewed in this article. An understanding of the tick vectors, pathogenesis, epidemiology, clinical presentation, diagnosis and treatment is useful for the clinician treating patients potentially infected with any of these pathogens. Prevention measures, the optimal method for removing an attached tick and current and future vaccine development conclude this review.