In the last decade, the medial sural artery perforator flap (MSAP) has emerged as one of the most popular reconstructive options for multiple body sites. The versatility of the flap hinges on the ability to harvest multiple tissue components in various combinations but from the same wound. The flap can be used as a pedicled, free, or chimeric design, or even may be used in sequential order. Anatomic anomalies of these perforators are rare compared with other perforator flaps, but well-prepared preoperative planning and the identification of perforators remain the cornerstone of successful flap harvest. So far, the MSAP has been proved to be an excellent alternative for skin resurfacing and functional reconstruction in head and neck as well as in the extremities. In this review, the anatomy, preoperative planning and flap design, harvest technique, and its clinical application in multiple body sites are summarized. Both the advantages and disadvantages are also included.