The safety demonstration and validation of autonomous vehicles (AVs) remains a challenging activity. In this paper, we firstly review what those challenges are and how they affect the safety validation of the AV. Then, we particularly focus on the simulation-based validation process, which seems to be inevitable among the recommended safety validation approaches. We show what is actually done and required in terms of scenarios generation, their assessment taking into account uncertainty and the simulation architecture to test and validate them. Finally, we end our review by summarizing key research questions that need to be addressed to help with this safety validation issue.