Today phase refinement is trusted to electron-density modification (EDM) techniques, and in practice to dual-space methods which try, via suitable constraints in direct and in reciprocal space, to generate higher quality electron-density maps.  The most popular EDM approaches, denoted here as mainstream methods, are usually part of packages which assist crystallographers in all of the structure-solution steps from initial phasing to the point where the molecular model perfectly fits the known features of protein chemistry. 
EDM
The most popular EDM approaches, denoted here as mainstream methods, are usually part of packages which assist crystallographers in all of the structure-solution steps from initial phasing to the point where the molecular model perfectly fits the known features of protein chemistry.  Other phase-refinement approaches that are based on different sources of information, denoted here as out-of-mainstream methods, are not frequently employed.  This paper aims to show that mainstream and out-of-mainstream methods may be combined and may lead to dramatic advances in the present state of the art. 
mainstream methods
Other phase-refinement approaches that are based on different sources of information, denoted here as out-of-mainstream methods, are not frequently employed.  This paper aims to show that mainstream and out-of-mainstream methods may be combined and may lead to dramatic advances in the present state of the art. 
out-of-mainstream methods