This chapter reviews other approaches and technologies that have been applied to stratum corneum (SC) barrier disruption and how they compare to microneedles. Indirect physical methods involve the application of an energy source to the skin surface to increase diffusivity of an applied solute in the SC. Enhancement techniques include vehicle modification to include chemicals capable of enhancing solute solubility in the SC and directly disordering the SC lipid domains, and nano and microemulsion and vesicle formulations. Sonophoresis is the application of acoustic waves to facilitate transdermal delivery. Microdermabrasion was initially developed as a technique for skin rejuvenation via superficial disruption of the skin as is utilized in dermatological and cosmeceutical practices. The original biolistic particle delivery system, or gene gun, was designed for delivering exogenous DNA into plant cells. Microneedles act to create pores through the SC to provide direct access to the viable epidermis and are particularly effective for enhanced delivery of hydrophilic compounds.