This chapter seeks to familiarize the readers with tick-borne diseases. Rickettsia rickettsii is the cause of Rocky Mountain spotted fever (RMSF) and is the prototype bacterium in the spotted fever group of rickettsiae. For diagnosis, serologic testing is unreliable early during the course of infection. Lyme disease (LD), also known as borreliosis and Bannwarth syndrome, is an infection caused by the bacterium Borrelia burgdorferi (the spirochete), which is carried and spread by several types of ticks. It can be passed to humans when ticks feed on infected animals, become infected themselves and then bite people. Relapsing fever is characterized by recurrent acute episodes of fever, followed by periods of defervescence of increasing duration. Diagnosis can be made from blood smear as evidenced by the presence of spirochetes. Babesiosis is a tick-borne protozoal infection due to Babesia microti species of intraerythrocytic protozoa. PCR is the preferred method for diagnosis on whole blood specimen, which is more sensitive than direct microscopy. Both human monocytic ehrlichiosis (HME) and human granulocytic anaplasmosis (HGA) are clinically similar to tick-borne rickettsial diseases. Treatment should be initiated when infection is suspected because treatment delays are associated with poorer outcomes. The Borrelia miyamotoi disease (BMD) can cause more severe symptoms than lyme disease. Doxycycline is recommended as first-line treatment of suspected BMD.