This article provides an update of liver-directed gene therapy for dyslipidemia, reviewing papers published since 2002 and summarizing progress in gene transfer vectors. Despite the availability of polypharmacy and other therapeutic interventions, the treatment of severe dyslipidemia remains a challenge and continues to be an important target for experimental gene therapy. Gene therapy strategies that focus on long-term therapeutic efficacy of different regimens are emerging from small animal experiments, and new therapeutic genes and/or new approaches have been developed. A novel strategy for gene therapy for diabetes was published recently. Gene therapy for dyslipidemia and diabetes is still in its infancy. Nonetheless, recent progress in this area is encouraging and bodes well for the future.