What are the stumbling blocks for achieving high-efficiency organic photovoltaic devices? This question is examined from a molecular architecture and molecular packing perspective. The intermolecular interaction between the electron donor and electron acceptor influences the charge separation. The packing of electron donors and acceptors influences the charge transport. Therefore, there is a need to strike a balance between the charge-transfer interactions and packing interactions and obtain nanoscale segregated morphologies for efficient charge separation and charge transport. Molecular architecture is key toward striking this balance and, therefore, its impact on charge-transfer interactions and packing interactions; thus, the active-layer morphology and photovoltaic metrics are examined. A variety of molecular architectures for the packing of π-conjugated organic molecules to structures relevant for photovoltaic devices is also discussed.