Healing of pilonidal sinus wounds (PSWs) by secondary intention requires an average of 2 to 6 months, but delayed healing may require 1 to 2 years or even longer. Characteristically, these midline wounds are in the natal cleft of the buttocks or sacrococcygeal area of the back. These PSWs have costly financial consequences to the healthcare system and negatively affect the quality of life of the individual with the wound. This article contains an evidence-based literature review supplemented by the clinical expert opinion of the authors. Twelve leading mistakes in assessment and treatment have been identified with appropriate solutions to optimize patient outcomes. A case study is included to illustrate the common clinical challenges with strategies to optimize healing.