A general overview for the process development and manufacturing of engineered drug particles by size reduction techniques is provided. Drug compound and drug product characteristics are reviewed, which may need an engineered drug particle size. Drug particle attributes are introduced which are affected by size reduction techniques and potentially require additional downstream processing effort. The development of drug particle size specifications is described, including adequate size control. A brief overview is given on dry- and wet-milling technologies currently applied in drug development and manufacturing, including selected application examples. Finally, the processing of highly active drug compounds is introduced with respect to equipment design, worker protection, cleaning and waste management to minimize worker exposure and environmental impact.