Abstract Life cycle assessment (LCA) is one of the widely used tools to assess the environmental impacts of a product and or processes. Results from LCA are used to compare different products, and many scientific insights can be gained from a well-executed LCA study. Comparative studies made out of an LCA study can be used to make many important business decisions such as purchase decisions, sourcing options, etc. However, everything depends on the scientific validity of a particular study and how far the results are justified by means of a well-defined methodology and the scope of the work. Well-defined and executed studies can be used in such decisions. In the world of textiles, there always lies a dilemma and a tug of war between natural and man-made (or synthetic) textiles in terms of functional properties, comfort properties and very importantly ecological or environmental impacts made by these two extreme types of textiles. It is a very tough call to conclude which one is ecologically sound, once having been given the two options, and only a scientific study like LCA can answer this. Again, we cannot compare two different studies executed under different conditions. We need a study on a uniform platform that evaluates both types of textiles with a unique lens. Such studies are very limited, and there is a dire need for such studies in the world of textiles. This chapter highlights all these aspects along with discussing the limited available case studies on comparative assessment of natural and man-made textiles.