During the last two decades, the imaging landscape of multiple myeloma (MM) has evolved with whole-body imaging techniques such as fluorodeoxyglucose positron emission tomography-computed tomography (F-FDG PET/CT) and MRI replacing X-ray skeletal survey. Both imaging modalities have high diagnostic performance at the initial diagnosis of MM and are key players in the identification of patients needing treatment. Diffusion-weighted MRI has a high sensitivity for bone involvement, while F-FDG PET/CT baseline parameters carry a strong prognostic value. The advent of more efficient therapeutics, such as immunomodulatory drugs and proteasome inhibitors, has called for the use of sensitive imaging techniques for monitoring response to treatment. Diffusion-weighted MRI could improve the specificity of MRI for tumor response evaluation, but questions remain regarding its role as a prognostic factor. Performed at key time points of treatment in newly diagnosed MM patients, F-FDG PET/CT showed a strong association with relapse risk and survival. The deployment of minimal residual disease detection at the cellular or the molecular level may raise questions on the role of these imaging techniques, which will be addressed. This review summarizes and outlines the specificities and respective roles of MRI and F-FDG PET/CT in the management of MM.