Musculoskeletal imbalances or pathologies often develop into secondary physical conditions or complications that may affect the mobility and quality of life of people with lower-limb amputation. Using one or more prostheses causes people with amputation to alter the biomechanics of their movement. For example, people with lower-limb amputation often favor and stress their intact lower limb more during everyday activities. This can lead to degenerative changes such as osteoarthritis of the knee and/or hip joints of the intact limb. Since people with amputation spend less time on their residual limb, osteopenia and subsequent osteoporosis often occur secondary to insufficient loading through the long bones of the lower limb. A proper prosthetic fit increases the probability of equal force distribution across the intact and prosthetic limbs during ambulation, thus decreasing the risk of osteoarthritis. People with limb loss commonly complain of back pain, which is linked to poor prosthetic fit and alignment, postural changes, leg-length discrepancy, amputation level, and general deconditioning. We review the literature on secondary complications among people with lower-limb loss who are long-term prosthesis wearers.