Approximately 900 tick species exist worldwide, and they parasitize a variety of mammals, including humans; thus, ticks play a significant role in the transmission of infectious diseases. In the United States, tick-borne diseases are seasonally and geographically distributed; they typically occur during spring and summer but can occur throughout the year. Tick-borne diseases are endemic to a variety of geographic regions of the United States, depending on the species of tick commonly found in a specific locale. Specific tick-borne diseases are difficult to diagnose. Most patients have vague constitutional symptoms and nonspecific laboratory findings. Initially, serologic methods are of little benefit because they lack sensitivity early in the disease course. Therefore, a thorough history and physical examination are necessary for establishing a diagnosis. Antimicrobial regimens for tick-borne infections are poorly studied but well established. Tetracyclines and rifampin form the cornerstones of therapy for most tick-borne infections, but these agents may not be suitable for all patient populations. Therefore, no single agent can be chosen empirically to treat all tick-borne diseases. Because pharmacists are the most accessible health care providers, they are often asked how to treat tick-borne diseases. Thus, practitioners should be familiar with the ticks that inhabit their locale.