Photodynamic therapy (PDT) is a highly specific and clinically approved method for cancer treatment in which a nontoxic drug known as photosensitizer (PS) is administered to a patient. After selective tumor irradiation, an almost complete eradication of the tumor can be reached as a consequence of reactive oxygen species (ROS) generation, which not only damage tumor cells, but also lead to tumor-associated vasculature occlusion and the induction of an immune response. Despite exhaustive investigation and encouraging results, zinc(II) phthalocyanines (ZnPcs) have not been approved as PSs for clinical use yet. This review presents an overview on the physicochemical properties of ZnPcs and biological results obtained both in vitro and in more complex models, such as 3D cell cultures, chicken chorioallantoic membranes and tumor-bearing mice. Cell death pathways induced after PDT treatment with ZnPcs are discussed in each case. Finally, combined therapeutic strategies including ZnPcs and the currently available clinical trials are mentioned.