Suspension-based long-acting injectables (LAIs) are gaining momentum in the pharmaceutical industry due to their ability to deliver sustained therapeutic effects of relatively high dosed compounds. This chapter explores some of the elements related to industrial applications of aqueous suspensions for LAI applications, including discussions on manufacturing methods and development challenges. Dry and wet size reduction methods are commonly used for producing micro- and nanosuspensions. However, emerging bottom-up techniques offer new opportunities for particle engineering. LAIs have found success in treating schizophrenia, human immunodeficiency virus and other conditions, with several FDA-approved products and ongoing clinical trials. Despite their benefits, LAIs face challenges related to process development, in vitro–in vivo correlations (IVIVCs) and manufacturing scale-up. Addressing these issues requires a multidisciplinary scientific and organizational approach, combining formulation development, process optimization, robust IVIVC development and innovative analytical tools. A key to the success of LAIs lies in understanding the factors that impact product quality, such as stabilizer selection, equipment design and process parameters.