Internal carotid artery blood blister-like aneurysms are challenging lesions that arise from the artery trunk at non-branching sites. They have been recognized since 1969 and are distinct from typical saccular aneurysms. Usually, these aneurysms are broad-based, with no clearly identifiable neck and have extremely friable and fragile walls, thus with a great propensity to cause subarachnoid hemorrhage and to rupture during treatment. Apparently, blister-like aneurysms are formed through an acquired defect of the inner layers (tunica intima and media) of the internal carotid artery wall, probably due to hemodynamic stress in the carotid siphon.Several surgical and endovascular techniques have been described for the treatment of these aneurysms, however, there is still no consensus on the best technique or method, exposing how challenging the treatment of internal carotid artery blister-like aneurysms is, for both neurosurgeons and neurointerventionists. In this chapter, we review the main aspects of the pathogenesis, diagnosis, and therapeutics and report our experience in the microsurgical treatment of these formidable lesions.