Rocky Mountain spotted fever (RMSF), a potentially fatal, tick-borne disease caused by the gram-negative intracellular bacterium Rickettsia rickettsii, is endemic in parts of North and South America, especially the southeastern and southcentral United States. Although it was first recognized >100 years ago, the disease remains difficult to diagnose because a rash does not appear until an average of 3 days into the illness, and does not manifest a petechial or purpuric character until later in the course, if at all. Common presenting symptoms include fever, headache, myalgias, and gastrointestinal disturbances. The mortality rate associated with RMSF is 20% to 25% if untreated, and 5% with appropriate antibiotic therapy (if not initiated early enough). Treatment with doxycycline may be preferable to chloramphenicol therapy, because the tetracyclines have been shown in a retrospective study to be associated with a higher survival rate. Physicians must maintain a high index of suspicion for RMSF in patients with febrile illness and a history of potential tick exposure who present in the spring through the fall.