The pathophysiology of myocardial infarction (MI) and its management continue to evolve from systemic thrombolysis in the 1980s to systematic percutaneous coronary intervention in the 2000s. The current focus is on microvascular preservation. The pain-to-balloon time remains the overwhelming factor. Microvascular obstruction assessment with the index of microvascular resistance (IMR) obtained with bolus thermodilution has limited clinical utility because during an MI, the raised left ventricular end-diastolic pressure (LVEDP) confounds it. On the other hand, aggressive medical therapy, which reduces both blood pressure and LVEDP, has potential in limiting infarct size. Continuous thermodilution post-MI even in a poor but compensated LV can demonstrate preserved microvascular function after a large MI. Further, the drug-coated balloon reduces stenting during an MI, which ameliorates stent-related embolisation, avoids side-branch occlusion, and spares long-term endothelial dysfunction, hence theoretically improving left ventricular remodelling. This undoubtedly will be evaluated in future trials, but early anecdotal experience appears to support this thesis. MI with non-obstructive coronary arteries (MINOCA), at least in men, the majority of cases are due to plaque pathology, contributed by the synergistic triad of high cholesterol, smoking and blood pressure surges from physical and mental stresses, which in the setting of a stiff vessel, can disrupt the vascular endothelium, even in the absence of a vulnerable plaque, leading to a tear that extends to the media layer, thus precipitating coronary vasospasm. This could be one underappreciated mechanism in young men who smoke presenting with a cardiac arrest. Smoking demonstrably is associated with endothelial dysfunction, provable with acetylcholine and coronary flow estimation.