Recent advances in crystallographic computing have made it possible to solve by powder diffraction methods structures that have not been possible to solve by single-crystal methods. Although there is vast improvement in the quality of data obtained from high-intensity synchrotron radiation, we found that surprisingly reliable results can be obtained from conventional laboratory sources. In this article we examine the application of Monte Carlo/simulated annealing methods for the determination of structures ranging in complexity from 9 to 15 degrees of freedom. We re-determine the structures of papaverine hydrochloride and erythromycin A dihydrate by the powder diffraction method and compare the structures to those determined by single-crystal diffraction methods. The structure of a metastable polymorphic form of acetohexamide, form B, is solved and examined spectroscopically. Its structure has not previously been solved by single-crystal techniques because of the small size of its crystals.