The development and implementation of successful transdermal devices for drug delivery requires an understanding of the adhesion occurring between the device and the soft dermal layer. This study utilizes a mechanics approach to quantify the adhesive properties of representative pressure sensitive adhesives (PSAs) used as the adhesive layer in these systems. Debonding of PSAs is accompanied by cavitation in the PSA and the formation of an extensive cohesive zone behind the debond tip. The presence of such large-scale bridging provides significant energy dissipation and increased resistance to delamination. The strain energy release rate (G) during debonding of a cantilever-beam sample, containing at its midline a thin layer of PSA, was utilized to quantify the adhesion of the PSA. The analysis accounts for both the work of adhesion as well as the viscoelastic constitutive behavior of the soft adhesive layer. Effects of strain rate, physiological environment, and permeation-enhancement additions are considered. The resistance of human stratum corneum to debonding between corneocyte layers is also presented, as knowledge of this parameter is essential for developing techniques to test the fracture resistance of the PSA-stratum corneum interface present in the clinical use of these transdermal devices.