Although in the last few years emerging conventional and unconventional radiological and laboratory techniques have shed light on different pathophysiologic causes of stroke, nowadays almost 25% of ischemic strokes results of undetermined etiology. Different diagnostic criteria have been developed to define cryptogenic stroke and to establish its prevalence in stroke units. Different studies tried to unravel mechanisms of cryptogenic stroke and to evaluate adequate primary and secondary preventive measures, but standardized diagnostic and therapeutic strategies are still missing. In this review we report the most relevant updated notions in cryptogenic stroke providing an overview of the definition, the recommendations for diagnostic evaluation and the updated treatment strategies for secondary prevention.