The question of uncertainty has generated substantial critical engagements across the social sciences. While much of this literature falls within the domains of anthropology, science studies, and sociology, this short introductory paper highlights how geographical scholarship can also enrich emerging transdisciplinary debates on uncertainty. Specifically, we discuss how geographers engage with uncertainties produced through and reconfigured by some of the most formidable issues of our contemporary moment, including neoliberal transformation, disease and illness, resource conflict, global climate change, and ongoing struggles around knowledge, power, and justice. In conversation with debates in cognate fields, this special issue brings together contributions that grapple with uncertainty through key geographic concepts such as scale, power, spatiality, place, and human-environment relations. This work extends scholarly understanding of how uncertainty arises, is stabilized, and also how people navigate, experience, challenge, and rationalize uncertainty in everyday life. In doing so, we signal the immense potential offered by emerging intersections between human geography and broader critical social science interventions on the question of uncertainty.