It is readily apparent that there are varied topical and transdermal formulations and devices that have been developed, all of which have their own distinct features. Chemical approaches to topical and transdermal permeation modulation have been described in Chapter 3. However, the distinction and boundaries between “chemical” and “physical/technological” approaches (also known as “active” approaches) to permeation modulation are somewhat arbitrary; for example, there is certainly a degree of technological expertise used when preparing liposomal drug carriers which obviously use chemicals. However, the intention in this chapter is to examine strategies that reportedly physically or mechanically perturb or circumvent the stratum corneum barrier, such as microneedles, laser ablation, electroporation, or physically enhanced flux, such as iontophoresis. Other strategies that are considered include ultrasound (or sonophoresis), thermophoresis, needleless injection (the use of high-velocity particles), and the use of vesicular carriers. Whilst not an exhaustive list of permeation modulation strategies, the chapter covers the majority of approaches that have been, or that are currently being, researched and are not covered elsewhere.