Synthetic plastics are pivotal in our current lifestyle and therefore, its accumulation is a major concern for environment and human health. Petroleum-derived (petro-)polymers such as polyethylene (PE), polyethylene terephthalate (PET), polyurethane (PU), polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC) are extremely recalcitrant to natural biodegradation pathways. Some microorganisms with the ability to degrade petro-polymers under in vitro conditions have been isolated and characterized. In some cases, the enzymes expressed by these microbes have been cloned and sequenced. The rate of polymer biodegradation depends on several factors including chemical structures, molecular weights, and degrees of crystallinity. Polymers are large molecules having both regular crystals (crystalline region) and irregular groups (amorphous region), where the latter provides polymers with flexibility. Highly crystalline polymers like polyethylene (95%), are rigid with a low capacity to resist impacts. PET-based plastics possess a high degree of crystallinity (30–50%), which is one of the principal reasons for their low rate of microbial degradation, which is projected to take more than 50 years for complete degraded in the natural environment, and hundreds of years if discarded into the oceans, due to their lower temperature and oxygen availability. The enzymatic degradation occurs in two stages: adsorption of enzymes on the polymer surface, followed by hydro-peroxidation/hydrolysis of the bonds. The sources of plastic-degrading enzymes can be found in microorganisms from various environments as well as digestive intestine of some invertebrates. Microbial and enzymatic degradation of waste petro-plastics is a promising strategy for depolymerization of waste petro-plastics into polymer monomers for recycling, or to covert waste plastics into higher value bioproducts, such as biodegradable polymers via mineralization. The objective of this review is to outline the advances made in the microbial degradation of synthetic plastics and, overview the enzymes involved in biodegradation.