It is now well established that omega-3 long chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA; 20:5∆5,8,11,14,17) and docosahexaenoic acid (DHA; 22:6∆4,7,10,13,16,19) are important constituents of human nutrition and have key roles in growth and development of infants and children and in maintaining health through their effects on immune system. Although marine fish are the main dietary source of EPA and DHA, the depletion of fish stocks and pollution of the marine environment indicate an urgent need for an alternative and sustainable source of omega-3 LC-PUFAs. Marine microorganisms are the primary producers of omega-3 LC-PUFAs in the aquatic food chain and EPA- and DHA–rich microalgae have been demonstrated to be a promising alternative source to fish oils. However, the efficient production of high value products such as EPA and DHA from algae is expensive and significant efforts in strain development and cultivation technologies are still required to reduce the currently high production costs associated with algal biomass. Therefore, there is increasing interest in the metabolic engineering of microalgae and genetic modification of algal strains is considered to be one of the most promising strategies to produce new sustainable omega-3 oils. This review describes the recent advances in metabolic engineering of microalgae towards optimizing the production of omega-3 LC-PUFAs.