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Polymeric microparticles (MPs) are recognized as very popular carriers to increase the bioavailability and bio-distribution of both lipophilic and hydrophilic drugs. Among different kinds of polymers, poly-(lactic-co-glycolic acid) (PLGA) is one of the most accepted materials for this purpose, because of its biodegradability (due to the presence of ester linkages that are degraded by hydrolysis in aqueous environments) and safety (PLGA is a Food and Drug Administration (FDA)-approved compound). Moreover, its biodegradability depends on the number of glycolide units present in the structure, indeed, lower glycol content results in an increased degradation time and conversely a higher monomer unit number results in a decreased time. Due to this feature, it is possible to design and fabricate MPs with a programmable and time-controlled drug release. Many approaches and procedures can be used to prepare MPs. The chosen fabrication methodology influences size, stability, entrapment efficiency, and MPs release kinetics. For example, lipophilic drugs as chemotherapeutic agents (doxorubicin), anti-inflammatory non-steroidal (indomethacin), and nutraceuticals (curcumin) were successfully encapsulated in MPs prepared by single emulsion technique, while water-soluble compounds, such as aptamer, peptides and proteins, involved the use of double emulsion systems to provide a hydrophilic compartment and prevent molecular degradation. The purpose of this review is to provide an overview about the preparation and characterization of drug-loaded PLGA MPs obtained by single, double emulsion and microfluidic techniques, and their current applications in the pharmaceutical industry.Graphic abstract.