Differential diagnosis of autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) in adolescents is difficult due to similar behavioral topography. For instance, restrictive, repetitive behavior, cognitive rigidity, anxiety, and avoidance contribute to impairment in social relationships and daily living skills in both conditions. The diagnostic picture for youth with ASD and/or OCD may be further clouded by high rates of co-occurring gender-diverse clinical concerns, attention-deficit/hyperactivity disorder, tic disorder, depression, and anxiety disorders With increased prevalence and improved identification of ASD, OCD, and gender-identity-related distress, more adolescents are seeking treatment. It is vital that providers are knowledgeable about best practices for diagnosing and treating these overlapping symptoms. This review describes the state of the literature regarding presentation and prevalence of ASD, OCD, and gender-identity concerns separately and as co-occurring phenomena. Sex differences and gender-diversity among individuals with ASD and OCD are also reviewed. We briefly describe evidence-based behavioral treatments for ASD, OCD, gender-identity-related distress as separate and co-occurring considerations. Recommendations for tailoring within these therapies and family involvement are discussed.