This article outlines the conceptual and empirical basis for an inference-based approach (IBA) to treating obsessive-compulsive disorder (OCD). The IBA considers that in most cases the obsessional process begins with an initial doubt (e.g., "Maybe my hands are not clean"; "Perhaps the door was not locked"; "There's a chance I made an error"; "I could have harmed someone") and that this doubt is a product of invalid reasoning. The IBA focus on initial doubt adds an extra upstream dimension to the current cognitive behavior therapy (CBT), which targets downstream appraisals, following on from the initial intrusion. Hence the aim of inference-based therapy (IBT) is to modify the reasoning narrative producing the doubt, and to return the person to the world of commonsense perception. IBT complements existing CBT and a case study illustrates the application of the IBT protocol. The IBA may be particularly useful in cases where belief in the initial probability of an obsessional doubt is strongly held and/or where consequences or appraisals following the doubt are absent or minimally associated with distress.