Greater unpredictability in childhood from the level of the caregiver-child dyad to broader family, home, or environmental instability is consistently associated with disruptions in cognitive, socioemotional, behavioral, and biological development in humans. These findings are bolstered by experimental research in non-human animal models suggesting that early life unpredictability is an important environmental signal to the developing organism that shapes neurodevelopment and behavior. Research on childhood unpredictability has surged in the past several years, guided in part by theoretical grounding from the developmental psychopathology framework (shaped largely by Dr. Dante Cicchetti’s innovative work). The current review focuses on future directions for unpredictability research, including probing intergenerational effects, the role of predictability in resilience, cultural and contextual considerations, and novel developmental outcomes that should be tested in relation to childhood unpredictability. We urge the integration of multidisciplinary perspectives and collaborations into future research on unpredictability. We also provide ideas for translating this research to real-world practice and policy and encourage high-quality research testing whether incorporating predictability into interventions and policy improves developmental outcomes, which would support further dissemination of these findings.