Amyloidosis is a heterogeneous acquired or hereditary disease, characterized by extracellular deposition of misfolded protein in the form of beta-pleated sheets (amyloid) fragments throughout the body. The amyloid can deposit in any tissue or organ in the body and can be localized (in one organ) or systemic (in multiple organs). The location and characteristics of the protein are related to the organ dysfunction. The systemic condition is relatively rare but can be life-threatening. The clinical manifestations of amyloidosis are varied and can affect multiple different organs and bodily functions. Musculoskeletal symptoms are common in the disease but are often overlooked and underdiagnosed. Orthopaedic manifestations are common in amyloidosis. Carpal tunnel syndrome (CTS) and spinal stenosis have been well described in association with amyloidosis and may proceed the diagnosis by many years. Other common orthopaedic symptoms include bone and join lesions. In this chapter, we review the incidence and presenting symptoms of common orthopedic manifestations associated with different subtypes of amyloidosis. We also outline the methods for diagnosing the disease and discuss current treatment strategies.