One factor that must be considered during drug development process is that various types of pharmaceutical manufacturing can alter the physical characteristics of the drug entity. These effects become particularly important during scale-up of processing operations, because new and unanticipated results can become manifest in systems of insufficient characterization. Any transformed drug substance or altered dosage form could exhibit an altered solubility or dissolution rate that might produce an undesirable bioavailability profile. Some of the more interesting mechanical manipulations that have the potential to yield problems include particle size reduction and compression, and such investigations are the focus of this minireview.