Lyme borreliosis (LB) and relapsing fever (RF) are zoonotic diseases that are caused by spirochetal bacteria belonging to the genus Borrelia. The agents are generally maintained in natural transmission cycles by vector ticks (exception: body louse) and reservoir hosts. Lyme borreliosis (synonym in North America: Lyme disease, LD) is the most frequently reported tick-borne disease in Europe and North America. It mainly affects skin, large joints, nervous system or heart and is considered a multi-system disorder. Relapsing fever manifests as recurrent febrile attacks accompanied by headaches, muscle and joint aches, interrupted by afebrile intervals. It mainly occurs in tropical and subtropical regions including North and South America, Africa, Asia, and South European countries. In this chapter we describe the genus Borrelia, the huge diversity that has become apparent in recent years, the geographical distribution of its species, and the complex genome that is reflected in the complex ecology and disease symptoms. We also give information on diagnostics and its challenges, therapy, and prophylactic measures.