To summarize available evidence on the potential utility of pretreatment with intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA) in acute ischemic stroke (AIS) patients with large vessel occlusions (LVO) who are treated with mechanical thrombectomy. Despite theoretical concerns of a higher bleeding risk with IVT pretreatment, there are no data showing increased risk of symptomatic intracerebral hemorrhage (sICH) in patients with LVO receiving bridging therapy (IVT and mechanical thrombectomy) compared with direct mechanical thrombectomy (dMT). Additionally, evidence from observational studies suggest lower rates of infarctions in previously unaffected territories and higher rates of successful reperfusion, with lower number of device passes, in patients receiving bridging therapy. There are substantial discrepancies in studies comparing clinical outcomes between dMT and bridging therapy that are directly related to the inclusion of patients with contraindications to IVT in the dMT group. Ongoing clinical trials will provide definitive answers on the potential additional benefit of IVT in LVO patients receiving mechanical thrombectomy. IVT and mechanical thrombectomy are two effective reperfusion therapies that should be used in a swift and noncompeting fashion in AIS patients. AIS patients with LVO and no contraindications for IVT should receive promptly rt-PA bolus followed by immediate initiation of mechanical thrombectomy as indicated by current international recommendations, unless future randomized controlled trials provide evidence to proceed differently.