After harvest, the fruit ripens and stem-end rot (SER) starts to develop, leading to significant fruit losses. SER is caused by diverse pathogenic fungi that endophytically colonize the stem during fruit development in the orchard or field and remain quiescent until the onset of fruit ripening. During the endophytic-like stage, the pathogenic fungus colonizes the phloem and xylem of the fruit stem-end; after fruit ripening, the fungus converts to a necrotrophic lifestyle, while colonizing the fruit parenchyma, and causes SER. The fruit stem-end is colonized not only by pathogenic fungi, but also by various nonpathogenic endophytic microorganisms, including fungi, yeast and bacteria. However, little is known about the fruit stem-end endophytic microbiome, which could contain new and existing biocontrol agents. To control fruit SER, treatments such as ripening inhibition, harvesting with the stem, application of chemical or biological fungicides, or physical control such as heat treatments, cold storage, or exposure to light have been suggested. This review focuses on the characterization of SER pathogens, the stem-end microbiome, and different pre- and postharvest practices that could control fruit SER.