Institutional Review Boards (IRBs) were developed in response to a historically demonstrated need for ethical guidance and accountability in research with human subjects. The inhumane and unethical treatment of prisoners of war and underrepresented populations in the pre-IRB era are the antithesis of today’s national and international acts, codes, and declarations. Over the last five decades of IRB-reviewed research, several concerns about the IRB process have been raised. In this editorial, we review common concerns regarding the scope and functioning of IRBs. We also review the updated federal Common Rule, effective January 2018, and discuss how some of the reviewed concerns will be addressed in the update. Lastly, we end with recommendations for collaborating with IRBs. These recommendations are not tips on how to circumvent the review process but rather reflective and action-oriented steps to engage the IRBs, which are allies, collaborators, and expert consultants in the research enterprise.