Acquired immunodeficiency syndrome (AIDS) results from infection with human immunodeficiency virus (HIV), producing an immunodeficient state and severe pathology across multiple organ systems. Musculoskeletal involvement is particularly prevalent in this population with both infectious and non-infectious complications encountered, but it is suggested that the latter will affect 72% of HIV-infected individuals. In this review we aim to provide an update on the imaging characteristics of the non-infectious manifestations. The conditions include HIV-related arthritis as well as various malignancies, myositis, anaemia, osteonecrosis, rhabdomyolysis, hypertrophic osteoarthropathy and therapy-related side effects. For the clinician, the diagnostic challenge lies in differentiating disease-related symptoms from therapy-related side effects, particularly when clinical and laboratory features can be non-specific. This is especially difficult following the widespread introduction of highly active anti-retroviral therapy (HAART). Imaging investigations and MRI in particular have proven vital for facilitating early diagnosis and enabling prompt treatment. Furthermore, wider availability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has allowed whole-body assessment for staging and treatment response of malignancy. Understanding the pathogenesis of the various conditions and recognising their imaging features is essential for the clinical radiologist.