This chapter discusses the challenges facing cross-disciplinary researchers and argues that recognizing them early in the research process increases the likelihood of a cross-disciplinary research team’s success. Based on work by the Toolbox Dialogue Initiative (TDI), the chapter urges cross-disciplinary practitioners to carefully define their research problems, questions, goals, and end products, and to enlist collaborators from other disciplines at the beginning of their process. Doing so will help researchers shed light on potential obstacles early in their process, which can improve efficiency by avoiding wasted time. Early interventions can help teams identify and negotiate difficulties, which promotes successful and effective integration. Disciplinary assumptions, differences in communication styles, variations in scale and/or scope of partner contributions, failure to holistically integrate, and an inability or unwillingness to share control of a project are just a few challenges teams may need to address. The chapter presents questions teams should ask before embarking on a cross-disciplinary research project and then offers reasons why researchers should consider engaging in cross-disciplinary activities, even given the hurdles they may face.