The impact of fossil-based plastics on human health and the environment is undeniable. The growing concern of citizens and the implementation of new governmental green regulations make it urgent to find new alternative polymers to traditional plastics. Polyhydroxyalkanoates (PHAs) are microbial polymers, produced intracellularly as an energy reserve under conditions of nutrient depletion and carbon (C) abundance. Despite its attractive properties, the industrial development of PHAs is limited by the high production cost. In this sense, the use of renewable and plentiful raw materials, such as starch-based agro-industrial wastes, can overcome this constraint. This chapter provides a comprehensive review of the various developments that have produced PHAs from a variety of feedstocks such as starch from cassava, potato, corn, wheat, or rice. In addition, other interesting alternatives to reduce production costs have been explored, such as the isolation of microorganisms with the ability to degrade starch or the use of genetic engineering to obtain a PHA-producing microorganism with the ability to degrade the feedstock directly, reducing the production process to a single step. Moreover, the role of extremophilic microorganisms is being evaluated to improve the efficiency and the productivity of the process. These approaches pave the way for a sustainable industrial process that meets regulatory requirements and circular economy principles.