There has been significant improvement in the care for acute ischemic stroke (AIS) including those with late arrival large vessel occlusion (LVO). The groundbreaking randomized clinical trials (RCT) demonstrated a highest level of evidence in medicine for the treatment and outcome of AIS with LVO up to 24 hours of symptoms, and is considered as a standard of care. The mortality and disabilities have diminished significantly over the last 10 years, especially after the results of multiple positive clinical trials in 2015 and 2018. State, local, and national leadership organizations also embraced and acknowledged the need for stroke system care. In this review, we will discuss the basic understanding of AIS triage and treatments based on positive RCT and American Heart Association (AHA) guidelines. This review will bring the audience up to date with the current state of AIS therapy by brief presentations of all positive RCT results which will act as platform that will be utilized for the triage and treatment of four real-life AIS with LVO patients in the emergency department. This review will also discuss our rationale of specific triage and treatment of cases, based on trials and AHA guidelines, to help consolidate the cognitive knowledge to the real-time management of AIS with LVO. Additionally, the author will discuss his perspectives in the care of AIS, which includes the importance of stroke education with secondary prevention. Finally, the review will focus on the continuous improvement of AIS care with enrollment of more patients for therapies beyond the scope of RCT and AHA guidelines as an out-of-the-box approach including initiations of innovative clinical research.