Swine play important roles as models of human disease. A combination of genetic modification with somatic cell nuclear transfer (SCNT) holds the promise of uncovering the pathogenesis of human diseases and then of developing therapeutic protocols. Unfortunately, the mechanism(s) of nuclear remodeling (a change in the structure of the nucleus) and reprogramming (a change in the transcriptional profile) during SCNT remains unclear. Incomplete remodeling is thought to cause lower cloning efficiency and abnormalities in cloned embryos and offspring. Here, we review the epigenetic regulatory and remodeling events that occur during preimplantation development of embryos derived from fertilization or SCNT, with a focus on DNA methylation and histone modifications. The discussion ends with a description of attempts at assisted remodeling of the donor somatic cell nucleus and the SCNT embryo.