Simulated moving-bed (SMB) technology is attracting increased interest for application to the separation of pharmaceuticals and fine chemicals, particularly to enantioseparations. Unlike the large-scale UOP Sorbex process, these small-scale units use a series of HPLC columns, and the volume of the connecting lines may become comparable to the volume of the columns. In this work the effect of extra-column dead volume on SMB performance is analyzed, with the aim of providing a conceptual framework to account for it. In particular, guidelines to design SMB operating conditions with nonnegligible extra-column dead volumes to achieve the desired separation performance are provided. These are quantitatively assessed through comparison with the results obtained using a detailed SMB model, which accounts for extra-column dead volumes. The model allows the extent and the role of extra-column band broadening due to the presence of dead volumes to be evaluated. A set of experimental results on a laboratory SMB unit is discussed in light of the theoretical findings.