Methanol and acetonitrile are the two most popular organic solvents to use in the mobile phase for reversed-phase liquid chromatography (LC) separations. Tetrahydrofuran is also used to a lesser extent. Why are these solvents the most popular ones? Are there alternative solvents that should be tried? This month's "LC Troubleshooting" examines these and some other aspects of solvent selection for LC.