This special issue explores challenges and opportunities confronting higher education related to leadership at a variety of levels and the creation of linkages between students, faculty, administration, and community stakeholders necessary to address the many “wicked problems” facing society. One common thread among all the papers is that higher education is being challenged to collectively reexamine and change the paradigms under which they operate. Each of the articles express explicitly or implicitly that change happens through relationships and negotiating boundaries. The papers in this issue explore the challenges of leadership and program development at different scales from student and faculty learning to institutional initiatives that span across an entire campus. The leadership, relationship development, and boundary crossing experiences presented in the papers in this issue address four primary themes—Interdisciplinary Team Building Strategies, Curriculum and Community Connections, Institution-Level Leadership and Perspectives, and Interdisciplinary Leadership and Scholarship Support. Each of the individual papers address a pressing need in interdisciplinary and transdisciplinary work for development of effective, situation-relevant methods for negotiating disciplinary and professional boundaries.