Stroke is a leading cause of disability worldwide. Cryptogenic strokes (CS) account for almost a quarter of ischemic strokes despite modern diagnostic evaluation. A working definition of CS based on stroke classification systems is essential for accurate conceptualization of this common entity. Mechanistic categories (potential paradoxical embolism; atherosclerotic disease of the aorta or supra-aortic vasculature; and occult arrhythmia) should aide in parsing the often heterogeneous mix of conditions included in the CS subtype. Despite efforts to unravel mechanisms of CS, specific or targeted recurrent stroke prevention strategies are lacking. For example, recent trials have shown no clear benefit of patent foramen ovale closure in stroke prevention after CS. There are promising ongoing clinical trials that will address appropriate diagnostic evaluations in CS as well as novel therapeutic interventions. Overall, a standardized approach must be framed to diagnose and manage patients with CS and guide clinical practice and future research.