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. 1 Introduction. An automated vehicle (AV) is a vehicle, which is able, according to the conditions of its operating environment and the level of automation, to move with or without human intervention. The Society of Automotive Engineers 1 (SAE) identifies six levels of automation: No Automation (Level 0), Driver Assistance (Level 1), Partial Automation (Level 2), Conditional Automation (Level 3), High Automation (Level 4), and Full Automation (Level 5). For its operation, an automated vehicle collects information about its environment, processes them, plans its trajectory and decides on actions to be performed. To implement this, manufacturers use specific technologies such as sensors and localization systems, communication systems and intelligent control systems. These embedded technologies are sometimes new, difficult to specify and have functional performance limitations regarding environmental conditions. This affects standard safety validation procedures, which face new challenges and are