This document serves as a resource for information on this current shortage and in the event of a future shortage. It addresses the impact on adult and pediatric patients by providing potential management strategies, pharmacotherapeutic considerations, and safety implications. Thrombolytics such as tenecteplase and alteplase are used for critical care conditions such as acute ischemic stroke (AIS), pulmonary embolism (PE), and ST elevation myocardial infarction (STEMI). Both tenecteplase and alteplase are on shortage due to increased global demand and challenging manufacturing processes. Alteplase should be reserved for acute PE because of the literature supporting increased efficacy whereas both alteplase and tenecteplase can be used for treatment of AIS. The recommendations provided in this document are based on both current evidence, including a review of available literature by the SCCM Drug Shortages and Medication Safety Committee, and the need for conservation during this shortage.