Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low cost, effective antimicrobial therapy. The greatest challenge to clinicians is the difficult diagnostic dilemma posed by these infections early in their clinical course, when antibiotic therapy is most effective. Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult. In October 2004, CDC's Viral and Rickettsial Zoonoses Branch, in consultation with 11 clinical and academic specialists of Rocky Mountain spotted fever, human granulocytotropic anaplasmosis, and human monocytotropic ehrlichiosis, developed guidelines to address the need for a consolidated source for the diagnosis and management of TBRD. The preparers focused on the practical aspects of epidemiology, clinical assessment, treatment, and laboratory diagnosis of TBRD. This report will assist clinicians and other health-care and public health professionals to 1) recognize epidemiologic features and clinical manifestations of TBRD, 2) develop a differential diagnosis that includes and ranks TBRD, 3) understand that the recommendations for doxycycline are the treatment of choice for both adults and children, 4) understand that early empiric antibiotic therapy can prevent severe morbidity and death, and 5) report suspect or confirmed cases of TBRD to local public health authorities to assist them with control measures and public health education efforts.