Rare and atypical musculoskeletal infections of the appendicular skeleton, such as leprosy, cat-scratch disease, and atypical mycobacterial infections, often present with subtle or misleading clinical and radiological findings. These infections, though uncommon, may result in significant morbidity if not accurately diagnosed and treated. Advanced imaging modalities, particularly magnetic resonance imaging and computed tomography, play a critical role in identifying these conditions, distinguishing them from mimickers such as malignancies or autoimmune diseases, and guiding appropriate management. This chapter provides an in-depth analysis of these conditions, highlighting their pathophysiology, clinical features, imaging characteristics, differential diagnoses, and treatment options.