Open research practices are relevant to all stages of research, from conceptualization through dissemination. Here, we discuss key facets of open research, highlighting its rationales, infrastructures, behaviors, and challenges. Part I conceptualizes open research and its rationales. Part II identifies challenges such as the speed and cost of open research, the usability of open data and materials, the difficulties of conducting replication research, and the economics and sustainability of open access and open research generally. In discussing these challenges, we have sought to provide examples of good practice, describe and evaluate emerging innovations, and envision change. Part III considers ongoing coevolutions of culture, infrastructure, and behaviors and acknowledges the limitations of our review and of open research practices. We argue that open research is indeed a large part of our future, and most—if not all—challenges are surmountable, but doing so requires significant changes for many aspects of the research process.