Docosahexaenoic acid is a fatty acid found naturally in plants oil, fish oil, fish meat, seafood flaxseed, algae, and egg yolk. It is one of the long-chain unsaturated fatty acids that are important for human biochemistry. As an important component of grey matter, docosahexaenoic acid is subject to intense research in the field of neurodevelopmental study. It is needed mainly in the third trimester of pregnancy for optimal foetal brain growth and mother’s docosahexaenoic acid intake is known to be important in supplying the foetal needs. However, arguments still exist on whether docosahexaenoic acid status is essential or non-essential for infants, especially in the preterm infant population. In the past, strong arguments coming from translational studies showed the benefits of supplementation of docosahexaenoic acid in developing foetuses and infants. Hence, docosahexaenoic acid supplementation has long existed as commercially available docosahexaenoic acid-fortified formula milk. However, the benefit of this supplementation remains controversial after follow-up in human-based studies and clinical trials. The discovery of the fatty acid desaturase gene and its significance in regulating human docosahexaenoic acid and polyunsaturated fatty acids levels also seemed to give new evidence basis for docosahexaenoic acid supplementation in infants. This literature review attempts to explain the current understanding of clinical benefit of docosahexaenoic acid-fortified milk for infants, starting from the translational study level to clinical trials.