Left main (LM) coronary artery disease is a high-risk lesion subset, with important prognostic implications for the patients. Recent advances in the field of interventional cardiology have narrowed the gap between surgical and percutaneous approach of this complex lesion setting. However, the rate of repeat revascularization remains higher in the case of percutaneous coronary intervention (PCI) on long-term follow-up. As such, the need for better stent optimization strategies has led to the development of intravascular imaging techniques, represented mainly by intravascular ultrasound (IVUS) and optical coherence tomography (OCT). These techniques are both able to provide excellent pre- and post-PCI guidance. While IVUS is an established modality in optimizing LM PCI, and is recommended by international revascularization guidelines, data and experience on the use of OCT are still limited. This review paper deeply analyzes the current role of OCT imaging in the setting of LM disease, particularly focusing on its utility in assessing plaque morphology and distribution, vessel dimensions and proper stent sizing, analyzing mechanisms of stent failure such as malapposition and underexpansion, guiding bifurcation stenting, as well as offering a direct comparison with IVUS in this critical clinical scenario, based on the most recent available data.