Large business taxpayers are of critical importance to the economies in which they operate. They produce the majority of export income, provide a large share of the tax revenue and, in many economies provide the majority of jobs. They also have complex business structures with multiple operating entities that engage in international transactions presenting distinct and significant tax compliance issues that can have major consequences on tax revenues if not adequately addressed by tax administrations. In the wake of the work on the OECD/G20 project on Base Erosion and Profit Shifting (BEPS), which will provide tax administrators with new information and tools to address compliance issues related to this important taxpayer segment, it is incumbent upon tax administrations to ensure that their own actions do not create unnecessary tax uncertainty which could have negative consequences on economic growth and result in unpredictable government revenues. In this context, the issues surrounding tax certainty for both businesses and tax administrations will be of increasing importance. In this chapter, we will explore the current trends in managing large taxpayer compliance that focus on compliance risk management, international collaboration, co-operative compliance, and tax certainty.