MR offers powerful tools to measure molecular diffusion in intact tissues under in vivo conditions. This review focuses on the use of diffusion-weighted MR imaging (DW-MRI) and spectroscopy (DW-MRS) to noninvasively study structural and functional aspects of skeletal muscle. It will be shown that DW-MRI allows for a high-resolution reconstruction of the orientation of the muscle fibers, which represents vital input for mathematical models of muscle biomechanics and an improved understanding of contractile dysfunction in muscle disease. DW-MRS can be used to quantitatively measure the translational displacement of endogenous metabolites in intact muscle. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. This yields information on cellular architecture and on the intrinsic capacity for diffusional mass transport.