For individuals experiencing pain, the decision to engage in clinical trials may be influenced by a number of factors including current and past care, illness severity, physical functioning, financial stress, and caregiver support. Co-occurring depression and anxiety may add to these challenges. The aim of this scoping review was to describe perspectives about clinical trial participation, including recruitment and retention among individuals with pain and pain comorbidities, including depression and/or anxiety. We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL databases. Study features, sample demographics, perspectives, barriers and/or motivations were collected and described. A total of 35 assessments were included in this scoping review with 24 focused on individuals with pain (24/35, 68.6%), 9 on individuals with depression and/or anxiety (9/35, 25.7%), and 2 on individuals with pain and co-occurring depression/anxiety (2/35, 5.7%). Barriers among participants with pain and those with depression included: research team's communication of information, fear of interventional risks, distrust (only among respondents with pain), too many procedures, fear of inadequate treatment, disease-life stressors, and embarrassment with study procedures (more commonly reported in participants with depression). Facilitators in both groups included: altruism and supportive staff, better access to care, and the ability to have outcome feedback (more commonly among individuals with depression). Individuals with pain and depression experience challenges that affect trial recruitment and retention. Engaging individuals with pain within research planning may assist in addressing these barriers and the needs of individuals affected by pain and/or depression. PERSPECTIVE: This review highlights the need to address barriers and facilitators to participation in clinical trials, including the need for an assessment of perspectives from underserved or marginalized populations.