The selection of media in dissolution method development can sometimes be an arbitrary decision. The case studies in this article give a practical rationale that should help in selecting media, especially surfactants. Three cases were studied: (1) the role of surfactants versus compound stability in the dissolution medium during dissolution method development, (2) the selection of a surfactant based on interactions between the dissolution medium and the drug substance, and (3) the selection of media based on formulation properties. In the first case study, the choice of surfactant in relation to solubility and physical stability of the drug substance is shown. The second revealed an unexpected synergy between polysorbate 20 (Tween) and acetic acid solution that caused an unusual increase in the dissolution rate compared with these media used separately. In the last case study, the medium was modified by addition of surfactant to reflect a change in the formulation. The selection of a dissolution medium should be based on drug substance and formulation characteristics as well as on interactions among components.