Patient-related barriers have hindered cancer patients' abilities to participate in the decision-making processes to participate in clinical trials. However, little is known about patients' emotional barrier of fear and how physicians influence this barrier. We conducted 48 in-depth interviews with cancer patients to determine their knowledge and attitudes about participating in clinical trials, transcribed interviews verbatim, and qualitatively analyzed the transcripts using content analysis. For the purpose of this manuscript, we focused on findings related to the role of the emotional barrier of fear in cancer patients' perceptions of participating in clinical trials. The majority of cancer patients (n = 40, 83.3%) discussed fears surrounding clinical trials, particularly as it related to cancer diagnosis, clinical trial participation, and fear of the unknown. In conclusion, providers might consider addressing the role of fear in patients' considering participating in a clinical trial.