Ticks may transmit a variety of human pathogens and are second in importance only to the mosquito as a vector of human disease. The majority of tick-borne diseases are nonspecific in their initial clinical and laboratory presentation and may be confused with a variety of more common illnesses. A history of tick exposure is frequently not available. Although specific serologic tests exist for confirming the diagnosis of many of these diseases, the time required for confirmation of results makes them of little use in the acute situation. Recognition of the epidemiology of tick-borne pathogens and clinical suspicion are of key importance in making the appropriate diagnosis. Early and specific therapy is a principal factor in reducing the morbidity and mortality associated with these diseases.