MNs, when used to puncture the skin, will by‐pass the stratum corneum and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. However, for effective performance of these MNs in drug delivery applications, irrespective of the type (hollow or solid), material, height and density of MNs, it is imperative that these needles penetrate into the skin with the greatest possible accuracy and reproducibility. But, due to the inherent elasticity and irregular surface of the skin, it remains a major challenge for reproducible MN arrays penetration. Therefore, in order to achieve uniform and reproducible MNs penetration into the skin, an external source of assistance is required such as an applicator device. Accordingly, this chapter deals with various innovative applicator designs developed and patented by different industries, and also by researchers from academia, in the context of effective application of MN arrays for transdermal drug delivery.