With a fascinating complexity, governed by multiple physiological processes, the skin is considered a mantle with protective functions which during lifetime are frequently impaired, triggering dermatologic disorders. As one of the most prevalent dermatologic conditions worldwide, characterized by a complex pathogenesis and a high recurrence, acne can affect the patient’s quality of life. Smart topical vehicles represent a good option in the treatment of a versatile skin condition. By surpassing the stratum corneum known for diffusional resistance, a superior topical bioavailability can be obtained at the affected place. In this direction, the literature study presents microemulsions as a part of a condensed group of modern formulations. Microemulsions are appreciated for their superior profile in matters of drug delivery, especially for challenging substances with hydrophilic or lipophilic structures. Formulated as transparent and thermodynamically stable systems, using simplified methods of preparation, microemulsions have a simple and clear appearance. Their unique structures can be explained as a function of the formulation parameters which were found to be the mainstay of a targeted therapy.