an improvement of critical features, including transcription, translation and post-translational modifications, in plant cells could make plant systems a safe and economical alternative for biopharmaceutical production. Hence, in this review, the most recent advances influencing the upstream and downstream processes involved in recombinant protein accumulation in plant cells are described. We also discuss how plant systems are becoming the benchmark for the production of several biopharmaceuticals.Keywords Heterologous expression · Host systems · Post-translational modifications · Plant-based pharmaceuticals · Recombinant protein identification and characterization of a promising regulatory pathway for the large-scale production of biopharmaceuticals could strongly contribute to the benefits of this system (Fischer et al. 2012). Molecular pharming technology presents several advantages, including (a) the production of low-cost biomass; (b) end-products lacking human toxicity; (c) the accumulation of complex proteins with correct and proper folding; and (d) straightforward methods for protein purification (Moustafa et al. 2015). Furthermore, molecular pharming offers a flexible, scalable and diverse alternative method for producing new, Abstract The use of plant systems as factories for recombinant protein production became a prominent alternative for pharmaceutical industries due to their high potential for protein accumulation. In the last decades, the application of plants for protein production has gained more attention, as plants represent an economic strategy that leads to high levels of purified and active proteins for the pharmaceutical sector. Currently, FDA approval of the first generation of recombinant proteins produced in carrot cells, taliglucerase alfa, demonstrated that plant cells have a significant capacity to express complex proteins for therapeutic use. Although plant systems still have technical and economic barriers that require improvements in future years, the optimization of upstream and downstream components affecting protein accumulation is considered a key feature in the development of new pharmaceutical proteins. Therefore,