This chapter examines the extent to which the external influences at the global, national and regional levels can inhibit regional engagement of higher education institutions and suggests adjustments to current policy and practice which could help to overcome these barriers. Barriers to regional engagement are addressed in a thematic manner starting with the sometimes conflicting effects of national higher education, science and technology and labour market policies. Particular attention is paid to how regional engagement is funded. The capacity of local and regional agents to engage with higher education institutions and the influence of regional governance and leadership is considered next. Finally, the chapter closes with reference to leadership at the level of the individual higher education institution.