Presented are three case studies in which twin screw extruders were utilized as a process chemistry tool to support the development of various drug substance programs. Through these investigations, twin screw extrusion (TSE) was found to be a versatile process to support an array of applications, including form screening, salt generation via green chemistry, and the isolation of the amorphous form for an active pharmaceutical ingredient (API) on a large scale. Case study I: 1 is an API where several unsolvated polymorphs were discovered and investigations of these phases were required to identify the stable form at room temperature. To support this, TSE was utilized to apply mechanochemistry for the scale-up of several of these polymorphs. Solubility measurements were then conducted to map their relative stabilities so that a crystallization could be designed to ensure polymorphic control. Case study II: 2 is an API that is a hemihydrated maleate salt, and TSE was applied on a powder blend of the freebase of 2 and maleic acid to generate the salt in an efficient, scalable, and environmentally friendly process compared to a traditional crystallization. Case study III: as opposed to its more traditional utility as a process to support amorphous drug product manufacturing, TSE was investigated as a novel way to generate an amorphous material for API 3 on a large scale (650 g) using a melt quenching process when more traditional routes like lyophilization or spray-drying methods were impractical.