Microporation of skin results in breaching the skin's stratum corneum barrier, thereby enhancing delivery of drugs of different physicochemical properties. However, application of microneedles (MNs) can be associated with the sensation of pain, erythema or both. Furthermore, by creating microchannels across the skin's stratum corneum, its barrier property is compromised, thus increasing the risk of invasion of exogenous materials (for example microorganisms), depending upon the MN dimensions. Additionally, the nature of material used in MN fabrication is also an integral component for its clinical application. In this chapter we discuss various clinical and safety parameters essential for widespread application of MNs.