Poly(lactic-co-glycolic acid) (PLGA) microparticles have been created to extend the duration of drug effects within the body. These delivery systems have found application in treating various chronic diseases. Despite the numerous advantages they offer in terms of treatment adherence, efficacy, and safety, only a limited number of formulations have gained approval and have reached the market. The manufacturing process for PLGA microparticles involves multiple steps and presents various challenges. Consequently, they are considered by pharmaceutical companies as complex formulations to develop. This chapter explores both established and innovative methods of manufacturing microparticles. It also delineates the manufacturing stages and the associated challenges in developing drug-loaded PLGA microparticles in a robust and well-controlled manner. In addition, aspects such as polymer type, drug release, drug loading, physicochemical properties of the encapsulated drug, sterilization, injectability and administration are discussed. Finally, a roadmap covering all the development stages is depicted.