With advances in molecular genetics, more pathogenic rickettsial species have been identified. Pathogenic rickettsiae are transmitted by vectors, such as arthropods, into the patient’s skin and then spread into the microvascular endothelial cells. Clinical manifestations are characterized by fever with headache and myalgias, followed by rash 3 to 5 days later. The undifferentiated nature of clinical symptoms, knowledge of the epidemiology, and the patient’s history of travel and exposure to arthropod vectors are critical to the empiric administration of antimicrobial therapy. Doxycycline is currently the most effective antibiotic for treatment of all spotted fever group and typhus group rickettsioses.