Ultraviolet C (UV-C, 200-280 nm) light has germicidal properties that inactivate a wide range of pathogenic and spoilage microorganisms. UV-C has been extensively studied as an alternative to thermal decontamination of fruit juices. Recent studies suggest that the efficacy of UV-C irradiation in reducing microorganisms in fruit juices is greatly dependent on the characteristics of the target microorganisms, juice matrices, and parameters of the UV-C treatment procedure, such as equipment and processing. Based on evidence from recent studies, this review describes how the characteristics of target microorganisms (e.g., type of microorganism/strain, acid adaptation, physiological states, single/composite inoculum, spore, etc.) and fruit juice matrices (e.g., UV absorbance, UV transmittance, turbidity, soluble solid content, pH, color, etc.) affect the efficacy of UV-C. We also discuss the influences on UV-C treatment efficacy of parameters, including UV-C light source, reactor conditions (e.g., continuous/batch, size, thickness, volume, diameter, outer case, configuration/arrangement), pumping/flow system conditions (e.g., sample flow rate and pattern, sample residence time, number of cycles), homogenization conditions (e.g., continuous flow/recirculation, stirring, mixing), and cleaning capability of the reactor. The collective facts indicate the immense potential of UV-C irradiation in the fruit juice industry. Existing drawbacks need to be addressed in future studies before the technique is applicable at the industrial scale.