Multiple scattering, modified fragmentation functions, and radiative energy loss of a heavy-quark propagating in a nuclear medium are investigated in perturbative QCD. Because of the quark mass dependence of the gluon formation time, the medium size dependence of heavy-quark energy loss is found to change from a linear to a quadratic form when the initial energy and momentum scale are increased relative to the quark mass. The radiative energy loss is also significantly suppressed relative to a light quark due to the suppression of collinear gluon emission by a heavy quark.