How do scientists maintain their research programs in the face of not finding anything? Continual failure to produce results can result in declining support, scientific controversy and credibility challenges. We elaborate on a crucial mechanism for sustaining the credibility of research programs through periods of non-detection: the maintenance of ambiguity. By this, we refer to scientific strategies that resist closure or an experiment’s premature end by creating doubt in negative findings and fostering hope for future positive results. To illustrate this concept, we draw upon the recent history of Martian exobiology. Since the 1960s, planetary scientists have continually tried and failed to find evidence of life on Mars. And yet, interest in extraterrestrial life detection remains high, with more missions to Mars underway. Through three destabilizing events of non-detection, we show how exobiologists sustained the search for Martian life by casting doubt on negative findings, pointing to other possible unexplored routes to success, and finally reconfiguring operations around new methods or goals. New approaches may take the form of shifts in scale, method and object of interest. By pivoting to a different scale, method or object, exobiologists have continued to study a subject continually lacking proof of existence and made important discoveries about life on Earth.