Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. The structure of the transport inhibiting outer layer, the stratum corneum, is temporarily destabilized due to the development of microscopic pores. Consequently agents that are ordinarily unable to pass into the skin are able to pass through this outer barrier. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with Joule heating. This paper shows the importance of using a composite model in calculating the electrical and thermal effects associated with skin electroporation. A three-dimensional transient finite-volume model of in vivo skin electroporation is developed to emphasize the importance of representing the skin’s composite layers and to illustrate the underlying relationships between the physical parameters of the composite makeup of the skin and resulting thermal damage potential.