History of the discovery of poly (ADP-ribose) -- Discovery of the PARP superfamily and focus on the lesser exhibited but not lesser talented members -- The role of PARPs in DNA Strand Break Repair -- TIPs: Tankyrase Interacting Proteins -- PARP and Carcinogenesis -- Multitasking roles for poly(ADP-ribosyl)ation in aging and longevity -- Overview of PARP Inhibitor Design and Optimization -- Structure Based Design of PARP Inhibitors -- Preclinical chemosensitization by PARP inhibitors -- Classification of PARP inhibitors based on PARP trapping and catalytic inhibition, and rationale for combinations with topoisomerase I inhibitors and alkylating agents -- Radiosensitisation by poly(ADP-ribose) polymerase inhibition -- The vasoactivity of PARP inhibitors -- Synthetic lethality with Homologous Recombination Repair defects -- Targeting tumour hypoxia with PARP Inhibitors: Contextual synthetic lethality -- Other determinants of sensitivity -- Synthetic sickness with molecularly targeted agents against the EGFR pathway -- Disruption of DNA repair by cell cycle and transcriptional CDK inhibition -- Resistance to PARP Inhibitors Mediated by Secondary BRCA1/2 Mutations -- PARP inhibitor resistance - what is beyond BRCA1 or BRCA2 restoration -- Introduction to PARPi clinical trials and future directions -- Clinical trials investigating PARP inhibitors as single agents -- Clinical trials of PARP inhibitors with chemotherapy -- Combination of PARP inhibitors with clinical radiotherapy -- Biomarkers for PARP Inhibitors.