Cancer is caused by the accumulation of genetic alterations and therefore has been historically considered to be irreversible. Intriguingly, several studies have reported that cancer cells can be reversed to be normal cells under certain circumstances. Despite these experimental observations, conceptual and theoretical frameworks that explain these phenomena and enable their exploration in a systematic way are lacking. In this review, we provide an overview of cancer reversion studies and describe recent advancements in systems biological approaches based on attractor landscape analysis. We suggest that the critical transition in tumorigenesis is an important clue for achieving cancer reversion. During tumorigenesis, a critical transition may occur at a tipping point, where cells undergo abrupt changes and reach a new equilibrium state that is determined by complex intracellular regulatory events. We introduce a conceptual framework based on attractor landscapes through which we can investigate the critical transition in tumorigenesis and induce its reversion by combining intracellular molecular perturbation and extracellular signaling controls. Finally, we present a cancer reversion therapy approach that may be a paradigm-changing alternative to current cancer cell-killing therapies.