Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier properties of the skin, mainly stratum corneum (SC), the delivery of many therapeutic agents across the skin has become challenging. Few drugs with specific physicochemical properties (molecular weight <500 Da, adequate lipophilicity, and low melting point) can be effectively administered via transdermal route. However, delivery of hydrophilic drugs and macromolecular agents including peptides, DNA and small interfering RNA is challenging. Drug penetration through the SC may involve bypass or reversible disruption of SC layer by various means. Recently, the use of micron-scale needles has been proposed in increasing skin permeability and shown to dramatically increase permeation, especially for macromolecules. Microneedles (MNs) can penetrate through the SC layer of the skin into the viable epidermis, avoiding contact with nerve fibers and blood vessels that reside primarily in the dermal layer. This review summarizes the types of MNs and fabrication techniques of different types of MNs. The safety aspects of the materials used for fabrication have been discussed in detail. Biological applications and relevant phase III clinical trials are also highlighted.