Introduction. In a recent meta-analysis we found no evidence that an antidepressant plus an antipsychotic is more effective than an antidepressant alone in unipolar psychotic depression. However, most current guidelines recommend the combination over an antidepressant alone. Method. We assessed available guidelines by the AGREE instrument and discuss their recommendations in relation to the evidence as referred to in the guidelines. Results. The UK-NICE guideline had the highest AGREE quality score, followed by the Dutch, Australian, and US-APA guidelines. Guidelines are not always consistent with at date of publication available evidence and (with exception of the UK-NICE and Dutch guidelines) also not with the in that guideline referred evidence. Conclusion. Physicians (and patients) should be aware that in guidelines treatment recommendations may be less evidence-based than asserted, even when treatment recommendations are stated as being based on the highest level of evidence.