Key Points Tick bites are typically painless, and most patients may be unaware of their tick exposure.Clinicians should ask early on about travel history and associated activities undertaken during travel to help determine if tick-borne illness should be included in the differential diagnosis.Clinicians should also be aware of the common clinical features of tick-borne illnesses in their local area to help differentiate between them and select appropriate testing and treatment.Serologic antibody testing, in the appropriate clinical setting, is often used to confirm tick-borne illness because the bacteria responsible for such infections are generally difficult—even dangerous—to culture.Specific treatment with doxycycline should be initiated for all age-groups as soon as Rocky Mountain spotted fever (RMSF) is considered as a possible diagnosis.