Clinical practice guidelines are used increasingly across medical specialties and settings, making evaluation of their utility and validity a critical public health issue. In this paper, we describe some of the challenges that specialty organizations face as they try to ensure that their guidelines are trustworthy and useful. We examine the practice guidelines for Major Depressive Disorder recently published by the American Psychiatric Association (APA), identify five sources of potential bias that may affect the guideline development process and offer suggestions based on our review. For example, even for mild depression, this guideline privileges pharmacotherapy over other interventions, despite questions about the risk/benefit ratio and the increasing concern over the iatrogenic harms of SSRIs and SNRIs. We compare recommendations from international scientific groups (e.g. NICE) with those produced by specialty societies in an effort to demonstrate some of the ways in which conflicts of interest, both intellectual and financial, may unduly influence guidelines.