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Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma (MM) from other monoclonal plasma cell diseases. Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity, limited specificity and its inability to detect extraosseous lesions. Besides conventional radiography, newer cross-sectional imaging modalities such as whole-body low-dose computed tomography (CT), whole-body magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM. Whole-body low-dose CT is used increasingly, replacing conventional radiography at selected centers, due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions. The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and (18)F-FDG PET/CT. According to current evidence, MRI is the most sensitive method for initial staging while (18)F-FDG PET/CT allows monitoring of treatment of MM. There is an evolving role for assessment of treatment response using newer MR imaging techniques. Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.