Obsessive-compulsive disorder (OCD) and illness anxiety disorder (IAD) often co-occur. Cognitive-behavioral models of both disorders overlap and include maladaptive attentional processes, misinterpretation of thoughts and physical sensations, and engagement in repetitive behaviors in an attempt to reduce associated distress. Given commonalities in their presentation and their common co-occurrence, it is important to understand how illness anxiety affects the presentation and treatment of OCD. In this article, theoretical conceptualizations of OCD and IAD and their comorbid presentation are outlined, and assessment and differential diagnosis of these conditions are discussed. Despite shared cognitive vulnerabilities and behavioral patterns, well-validated symptom measures, along with careful functional analysis, can be used to distinguish between OCD, IAD, and comorbid presentations. Best practices for the cognitive-behavioral treatment of these co-occurring conditions are also presented, with suggestions based on both the empirical literature and detailed case studies. Finally, recommendations for future research on co-occurring OCD and IAD and their treatment are explored.