Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible intracellular polyesters that are accumulated as energy and carbon reserves by bacterial species, under nutrient limiting conditions. Successful large-scale production of PHAs is dependent on three crucial factors, which include the cost of substrate, downstream processing cost, and process development. In this respect, design and implementation of bioprocess strategies for efficient PHA bioconversions enable high PHA concentrations, yields and productivities. Additionally, development of PHA fermentation processes using inexpensive substrates, such as agro-industrial wastes, facilitates further cost reduction, thus benefitting large-scale PHA production. Thus, the aim of this review is to highlight various bioprocess strategies for high production of PHAs and their novel copolymers in relatively large quantities. This review also discusses the application of kinetic analysis and mathematical modelling as important tools for process optimization and thus improvement of the overall process economics for large-scale production of PHAs.