Polyhydroxyalkanoates (PHAs) are biopolyesters accumulated as carbon and energy storage materials under unbalanced growth conditions by various microorganisms. They are one of the most promising potential substitutes for conventional non-biodegradable plastics due to their similar physicochemical properties, but most important, its biodegradability. Production cost of PHAs is still a great barrier to extend its application at industrial scale. In order to reduce that cost, research is focusing on the use of several wastes as feedstock (such as agro-industrial and municipal organic waste and wastewater) in a platform based on mixed microbial cultures. This review provides a critical illustration of the state of the art of the most likely-to-be-scale-up PHA production processes using mixed microbial cultures platform and waste streams as feedstock, with a particular focus on both, upstream and downstream processes. Current pilot scale studies, future prospects, challenges and developments in the field are also highlighted.