Targeting of PARP enzymes has emerged as an effective therapeutic strategy to selectively target cancer cells with deficiencies in homologous recombination signaling. Currently used to treat BRCA-mutated cancers, PARP inhibitors (PARPi) have demonstrated improved outcome in various cancer types as single agents. Ongoing efforts have seen the exploitation of PARPi combination therapies, boosting patient responses as a result of drug synergisms. Despite great successes using PARPi therapy, selecting those patients who will benefit from single agent or combination therapy remains one of the major challenges. Numerous reports have demonstrated that the presence of a BRCA mutation does not always result in synthetic lethality with PARPi therapy in treatment-naïve tumors. Cancer cells can also develop resistance to PARPi therapy. Hence, combination therapy may significantly affect the treatment outcomes. In this review, we discuss the development and utilization of PARPi in different cancer types from preclinical models to clinical trials, provide a current overview of the potential uses of PARP imaging agents in cancer therapy, and discuss the use of radiolabeled PARPi as radionuclide therapies.