Abstract
Rational drug development has come to psychiatry. Both the promise and the challenge that comes with this fact are great. One issue raised is whether to decide rationally to develop drugs with more than one mechanism of action (MOA) to improve efficacy and/or tolerability. As with any issue in science, thinking and planning will only take one so far. After that, the dice must be rolled and the results assessed. Undoubtedly, some drugs with dual or even more MOAs will prove to be desirable and others not. The question is which ones.