This chapter summarizes the development of π-conjugated polymers with donor-acceptor motifs that are based on a thiazolothiazole acceptor unit. We show that the crystallinity and backbone orientation of the polymers can be controlled by careful designing of the molecular structure. In-depth analysis of the orientation based on film thickness is also presented here. Further, the interplay between the polymers and various acceptors, which determines the crystalline order of materials in their blends, is systematically studied. Notably, the crystalline structures and backbone orientation correlate well with the photovoltaic performance. These findings will provide useful guidelines for the development of high-performance π-conjugated polymers for solar cells (organic photovoltaics).