It depends.
Sometimes you start writing a piece and realize it would be easier to play if you retuned one or two strings.
Sometimes you fiddle around and get to a tuning that inspires you.
I usually look for opportunities to have interesting intervals in adjacent strings (e.g. a 2nd or m7) for neat tensions or suspended chords, or dissonant intervals (b9, b5) on far apart strings (e.g. low D and high Eb). I find those dissonances are a lot less jarring when 2-3 octaves apart and make for interesting chord decorations.
The key is to not let the tuning write the song. Those always sound terrible and lazy.
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