Direct methods of phase determination have played an important role in determining heavy-atom substructures from difference amplitudes of native-derivative crystal pairs or crystals containing anomalously scattering atoms. The minimal principle-based Shake-and-Bake procedure is one of the most successful direct methods for heavy-atom substructure determination. The computer program SnB, which implements the Shake-and-Bake procedure and is part of the protein structure-determination package BnP, has recently been optimized for rapid and automated substructure determination. Specifically, SnB has been upgraded with (i) a newly developed statistical minimal function for higher success rates, (ii) an optimal FFT grid size for dramatic cost-effectiveness improvement, (iii) a dynamic figure of merit for automatic substructure-solution detection and (iv) a strategy of alternation of anomalous differences with isomorphous dispersive differences for virtually guaranteed substructure solution.