Inflammatory arthritis due to infection with Borrelia Burgdorferi is a well recognized clinical entity that also shares some features with other types of inflammatory arthritis, in particular rheumatoid arthritis. The diagnosis of arthritis due to Lyme disease rests upon eliciting a history compatible with known exposure to Ixodes daminii ticks that transmit the infection, the typical clinical features of Lyme arthritis, and serological testing. This article presents four patients with musculoskeletal syndromes related to Lyme disease and emphasizes the diagnostic approach to these patients with respect to distinguishing aspects of the history, physical examination, and laboratory testing.