Human skin is a multilayered physiochemical barrier protecting the human body. The stratum corneum (SC) is the outermost keratinized layer of skin through which only molecules with less or equal to 500 Da (Dalton) in size can freely move through the skin. Unfortunately, the conventional use of a hypothermic needle for large therapeutic agents is susceptible to needle phobia and the risk of acquiring infectious diseases. As a new approach, a microneedle (MN) can deliver therapeutically significant molecules without apparent limitations associated with its molecular size. Microneedles can create microchannels through the skin’s SC without stimulating the proprioceptive pain nerves. With recent technological advancements in both fabrication and drug loading, MN has become a versatile platform that improves the efficacy of transdermally applied therapeutic agents (TAs) and associated treatments for various indications. This review summarizes advanced fabrication techniques for MN and addresses numerous TA coating and TA elution strategies from MN, offering a comprehensive perspective on the current microneedle technology. Lastly, we discuss how microneedling and microneedle technologies can improve the clinical efficacy of a variety of skin diseases.