Biochemically, one-third of the collagen molecule is composed of glycine. The next largest amino acid component is formed by proline (PRO) and hydroxyproline, which together comprise approximately 23% of the collagen molecule. The best method to support wound collagen biosynthesis is to provide adequate host nutrition, assuring adequate provision of calories and protein. However, despite adequate nutrition, clinically, there is a need to enhance collagen synthesis and research has focused on methods to enhance collagen precursor availability. PRO biosynthesis is related to both the citric acid cycle and the urea cycle. During the early phases of wound healing, wound fluid PRO levels are at least 50% higher than plasma levels, suggesting active import of PRO into the wound. Providing additional PRO in the diet to enhance PRO bioavailability for collagen biosynthesis does not result in increased collagen accumulation. Provision of other citric cycle precursors such as glutamine also does not enhance wound collagen synthesis. In looking at other PRO biosynthetic pathways, the arginine (ARG) --> ornithine (ORN) --> glutamic semialdehyde --> PRO pathway looks the most promising. ARG administration in quantities above those required for growth and reproduction results in a marked enhancement in wound collagen deposition. This effect is also shared by ORN, which cannot replace ARG for growth requirement but shares many of its biological and pharmacological activities. Several mechanisms have been postulated to explain the positive effect of ARG on wound healing, although none have been firmly proven. In conclusion, ARG and ORN supplementation are most effective in increasing collagen deposition, but whether this is accomplished by conversion to PRO is uncertain.