Organic solar cells (OSCs) have developed progressively in efficiency over the last two decades. Though it is promising, this technology is still far from realizing its full prospect. One of the most important parameters that determine the efficiency of OSCs is the open-circuit voltage (VOC), which represents the maximum voltage a solar cell can provide to an external circuit. Light harvesting materials employed in OSCs have an optical band gap of around 1.7 to 2.1 eV and yet the VOC barely exceeds 1.0 V, which is approximately just half of the photon's original energy. By contrast, in inorganic counterparts such as Si, CIGS and GaAs, the difference is only 0.3 to 0.45 eV between the material bandgap and VOC. Hence, to achieve higher power conversion efficiencies (PCEs) in OSCs, a detailed understanding of the origins of VOC and the associated energetic loss mechanisms is indispensable. The presented review takes the opportunity to elaborate various governing mechanisms and factors affecting the VOC from a comprehensive yet insightful standpoint. This report also provides a concise synthesis of intricate interdependencies among the factors influencing VOC and highlights the potential research strategies to improve VOC, rendering possible pathways to facilitate the viable commercialization of OSCs.