Organic semiconductor materials are used in a variety of technologically important applications such as optoelectronic devices and thin-film transistors. The building blocks of organic semiconductors are often based on π-conjugated molecules. However, not all π-rich molecules exhibit favorable conductivities due to poor overlap between neighboring molecules. We discuss in this chapter our work to utilize crystal engineering strategies to direct the solid-state packing of organic semiconductor molecules and achieve favorable π-π stacking arrangements in hydrogen-bonded solids in the form of co-crystals. Co-crystal formers are employed to support face-to-face stacking of small-molecule organic semiconductor units (e.g. thiophenes). We also describe how co-crystallization can be used to direct solid-state reactions involving organic semiconductor molecules. Approaches involving metal-organic complexes to achieve conductivity are also discussed.