Objective: Due to migration, doctors see patients from different ethnic backgrounds. This causes challenges for the communication. To develop training programs for doctors in intercultural communication (ICC), it is important to know which barriers and facilitators determine the quality of ICC. This study aimed to provide an overview of the literature and to explore how ICC works. Methods: A systematic search was performed to find literature published before October 2012. The search terms used were cultural, communication, healthcare worker. A realist synthesis allowed us to use an explanatory focus to understand the interplay of communication. Results: In total, 145 articles met the inclusion criteria. We found ICC challenges due to language, cultural and social differences, and doctors' assumptions. The mechanisms were described as factors influencing the process of ICC and divided into objectives, core skills and specific skills. The results were synthesized in a framework for the development of training. Conclusion: The quality of ICC is influenced by the context and by the mechanisms. These mechanisms translate into practical points for training, which seem to have similarities with patient-centered communication. Practice implications: Training for improving ICC can be developed as an extension of the existing training for patient-centered communication.