This article highlights critical aspects of the epidemiology, diagnosis, and management of tick-borne infections in children. Principles that apply broadly across the continental United States are emphasized, rather than details of each disease. Tick-borne infections are often confused with other, more common childhood illnesses, in part because of their nonspecific initial clinical findings and because patients are usually unaware of their preceding tick exposures. This is a problem, because delays in starting appropriate antibiotic therapy increase the likelihood of adverse outcomes from these infections, especially Rocky Mountain spotted fever (RMSF). For patients in whom RMSF is a reasonable diagnostic consideration, therapy should be started presumptively, without awaiting the results of confirmatory diagnostic tests. For both adults and children, doxycycline is the drug of choice for RMSF and other American rickettsial infections. Concerns over the potential toxicity of doxycycline in young children are unfounded. Similarly groundless is the belief in “chronic Lyme disease” as an explanation for persistent nonspecific complaints after completing antibiotic therapy for Lyme disease. Prevention of tick-borne infections rests on avoidance of tick-bites and prompt removal of attached ticks. When used appropriately, insect repellents containing DEET are safe and effective for preventing tick exposures.