In general, there is a profound influence of reducing physical dimensions of particulates and devices on their physico-chemical and biological properties, and their performance. Reduction in the dimensions of hypodermic needle to micron-scale size has gained tremendous interest among researchers. Research efforts and publications investigating the design, development and applications of microneedles have exponentially increased in the recent years. Especially, microneedles have been widely studied and developed for cosmetic and therapeutic applications. Intense research efforts during the past decade have led to approval and commercialization of several microneedle based/assisted products for clinical use. Furthermore, numerous clinical trials aimed towards investigating the safety and efficacy of microneedle based systems are ongoing. The objective of this review is to provide an overview of completed and ongoing clinical studies performed using microneedle-based technologies for cosmetic, therapeutic and diagnostic applications. The review also provides a detailed overview of designs and applications of microneedle based devices that have been approved or are under clinical investigations. Clinical reports of microneedles for cosmetic applications including acne vulgaris, acne scars, skin rejuvenation and hair growth, and for therapeutic applications including influenza vaccination, polio vaccination, and diabetes are discussed in this review. Overall, this review—for the first time—provides a comprehensive overview of clinical efforts and outcome of microneedle based systems.