Parthanatos is a form of cell death, which often occurs in many diseases such as stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury. In a cell, the activation of PARP-1 caused by excitotoxicity leads to Parthanatos, which is also known as PARP-1-dependent cell death. There are multiple cell signaling pathways involved in the process of Parthanatos, which have not been fully understood. The main focus of this article is underlying molecular mechanisms of Parthanatos.