Frederick Perls's reflections on Salomo Friedlaender's theory of creative indifference and differential thinking, beginning with Ego, Hunger and Aggression, will be discussed. This approach emphasizes working with polarities and the zero-point (pre-difference), the significance of contextualization of our patient's suffering, and meaning-making. “Not-knowing” is an essential aspect of this attitude, which allows the uniqueness of every therapeutic situation to be explored and encourages experimenting and the reorganization of a dysfunctional field. If we are able to give up what is familiar to us, we may become anxious and uncertain, but then we can enter a “weighty world of nothingness” from which infinite and surprising differentiations can emerge. Experiencing this fertile void, or phase of pre-difference, is crucial to the creative process of change. Novel insights and realizations are generated, and we become aware of new meanings. This is the “middle mode,” in which we are both active and passive, both doer and done to.