Cross-border knowledge flows occur in many ways and are increasingly important for the world economy. In terms of international trade rules, knowledge flows are covered by different disciplines, both at the multilateral and at the plurilateral or bilateral levels. The purpose of this chapter is to provide a basic understanding of how such trade rules may affect cross-border knowledge flows. The chapter then discusses – particularly, in the light of new trends identified in recent plurilateral and bilateral agreements – whether the current multilateral disciplines are sufficient to regulate and encourage cross-border knowledge flows, or whether new trade rules to further promote such flows are needed.