Acute ischemic stroke (AIS) represents a critical neurological emergency requiring timely diagnosis and evidence-based intervention. Despite advancements in reperfusion strategies and imaging techniques, the management of AIS remains fraught with controversies. This chapter explores key areas of debate, including the choice and timing of neuroimaging, thrombolytic therapy beyond the traditional 4.5-h window, eligibility in elderly patients and those with comorbidities, use of tenecteplase versus alteplase, and thrombolysis in patients on direct oral anticoagulants. Additional areas of contention include rescue therapies following failed thrombectomy, optimal blood pressure targets post-intervention, and the role of dual antiplatelet therapy and genetic resistance. The chapter also evaluates diagnostic approaches to patent foramen ovale and examines evolving strategies in neuroprotection and anesthesia during endovascular therapy. Through a critical appraisal of current evidence and clinical guidelines, this chapter highlights the need for individualized treatment strategies and further research to resolve ongoing dilemmas in AIS management.