Chronic Lyme disease complex describes the burden carried by patients infected with Borrelia burgdorferi as well as other co-infections or secondary co-infections (opportunistic infections). These infections can cause a significant burden on patients more so than Lyme disease alone. Along with the many underdiagnosed cases of Lyme disease throughout the world exists numerous undiagnosed co-infection and secondary co-infections leading to debilitating symptoms for many patients. The potential for co-infections varies by location as well as to the exposure to various species of ticks. Since there is potential for patients to experience several tick bites including those of different species, additional microorganisms also commonly transmitted via tick bite are included that are typically left out of the conversation of potential Borrelia burgdorferi co-infections. The most common co-infections of Lyme disease include anaplasmosis, babasiosis, bartonellosis and ehrlichiosis. Secondary co-infections or opportunistic infections commonly seen in patients with Lyme disease are also discussed. By helping to establish a comprehensive list of infections associated with Chronic Lyme disease complex may in fact help patients receive a proper diagnosis in order to administer the much needed comprehensive treatments patients deserve.