In recent years, much attention has been focused on research to replace petroleum-based commodity plastics, in a cost-effective manner, with biodegradable materials offering competitive mechanical properties. Biopolymers have been considered as the most promising materials for this purpose. However, they generally present poor mechanical properties regarding processability and end-use application, since the fragility and brittleness exhibited during thermoformation can limit their potential for application. In order to overcome this problem, plasticizers are added to provide the necessary workability to biopolymers. This class of products became more visible when biodegradable additives and plasticizers also became the focus of material scientists. The use of natural and/or biodegradable plasticizers, with low toxicity and good compatibility with several plastics, resins, rubber and elastomers in substitution of conventional plasticizers, such as phthalates and other synthetic conventional plasticizers attracted the market along with the increasing worldwide trend towards use of biopolymers. Here we discuss the main results and developments in natural plasticizer/synthetic and biopolymer-based films during the last decades.