Lycopene is a terpenoid composed of 40 carbons characterized by its linear structure compared to other carotenoids. It has been attributed to important biological activities, mainly the antioxidant capacity against reactive oxygen species. In this area, it has been widely studied for the beneficial effects against cardiovascular diseases and some types of cancers, highlighting the significant number of studies that evidence the preventive effects on prostate cancer. Lycopene is widely distributed in nature over plants, animals, algae, and microorganisms. Over the years the growing application of lycopene has spread from the food and pharmaceutical industry to the formulation of supplements, nutraceuticals, and functional foods up to the cosmological industry for the development of products beneficial to the skin. In this sense, the main production of lycopene is done by chemical synthesis despite the environmental and safety implications. Another production alternative lies in plant sources, such as tomatoes. However, the quantities of lycopene recovered remain insufficient to meet the actual high demands. The microbiological synthesis of lycopene is an alternative that emerges as a more sustainable, ecological, and economic proposal. In nature, there is a wide variety of microorganisms studied for their ability to biosynthesize lycopene. One of the great challenges in this field evokes in the quantities of the carotenoid that are produced by the native metabolic pathways in the microorganisms. However, the optimization of these processes has evolved dramatically thanks to metabolic engineering, synthetic biology, and genetic engineering. The amount of lycopene recovered from plant sources is insufficient for the raw material processing. For its part, chemical synthesis is a rather complex and environmentally friendly methodology, as well as increasing the risk to consumer health. That is why this book chapter focuses on recent advances in the microbiological biosynthesis of lycopene, as well as some trends in metabolic and genetic engineering, as a more sustainable alternative in the production of red pigment.