Open-label placebos (OLP)-placebo pills honestly prescribed-have challenged the notion that placebos require either deception or concealment to evoke salubrious benefits. This essay describes how the author arrived at the counter-intuitive OLP hypothesis, discusses evidence for OLP effectiveness, and examines mechanistic explanations for OLP. Current dominant theories such as expectation and conditioning are found to be insufficient or inaccurate. The author proposes that emerging concepts of prediction and error processing (PEP), Bayesian brain, and embodied cognition are more appropriate models for understanding OLP. As a neural processing model, PEP argues that sensory predictions are embedded in and inseparable from perceptions; PEP circumvents mind-body dualism. The author discusses how OLP, mostly non-consciously, might perturb aberrant symptom amplifications and central sensitization resulting in perceptions of improvement in symptoms. Placebo effects are neurologically encoded predictions, less what patients think and more what they enact and perform.