Most individuals expect that healing is an inevitable outcome; wound healing is taken for granted. Although wound healing is perceived as inevitable, it can be fraught with problems and altered at many points. In the past, optimization of wound healing focused on minimizing contamination, accurate tissue approximation, and providing protection. With the advent of recombinant technology, optimization can now include manipulation of the molecular and cellular wound environment. Although the exact manipulative scheme has not yet evolved, it is clear from the multiple attempts reported in this article that understanding and progress is being made.