Polyunsaturated fatty acids (PUFAs) are key molecules for the control of human as well as animal health. Among the PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are vital compounds for infant brain development and other immune regulatory functions. Commercially available omega fatty acids are obtained from fish sources; nowadays fish oils are not preferred due to its unpalatable taste and odors as well as the fact that this resource is declining. Microalgae and other microorganisms based polyunsaturated fatty acids are gaining more attraction because of its fastest growth and lipids content; it is a preferred resource for vegetarians for omega 3/6 oils. Genetically modified organisms such as yeast are utilized for desired fatty acids production commercially. This chapter discusses the importance of polyunsaturated fatty acids for human health, various sources of PUFAs along with its fermentative productions and future perspective.