We discuss fundamentals and applications of the program "Powder Solve" that has been developed to solve crystal structures directly from powder diffraction data. The program uses a combination of simulated annealing and rigid-body Rietveld refinement techniques to find the trial structure giving maximal agreement between calculated and experimental powder diffraction data (assessed using the profile R-factor R-wp). Two examples are highlighted to demonstrate the application of Powder Solve for molecular crystals defined by up to 18 variable degrees of freedom.