External plasticization is a widely applied technique to improve PLA processability and toughness. Keys to successful plasticization of PLA are the miscibility of the plasticizer and its permanence in the polymer structure to ensure long-term stability of the material. To provide rules for successful plasticizing of PLA, a brief reminder of physicochemical mechanisms behind plasticization is given and the main theories allowing for the calculation of solubility parameters are summarized. To make use of this approach, a number of solubility parameters were gathered for potential PLA plasticizers. This chapter provides furthermore a comprehensive overview of literature results on glass transition temperatures and mechanical properties obtained for PLA and PLA nanocomposites mixed with monomeric and polymeric plasticizers. Additionally, physical and chemical long-term stability of plasticized materials is detailed. Finally, novel strategies of compounding PLA with additives derived from by-products of agriculture and food industries are discussed.