Apoptosis (programmed cell death), a self-destructive cellular mechanism, is essential for various events like sculpting the body, responding to any abnormalities, and removal of unwanted/damaged cells. Either too little or a high level of apoptosis causes conditions, such as chronic neurodegenerative maladies including Alzheimer's and Parkinson's diseases and cancer, i.e., an uncontrolled cell development. A typical apoptotic process includes cell shrinkage, degradation of DNA and mitochondrial breakdown, formation of blebs, cell fragmentation, release of nucleotides and phosphatidylserine on the surface of the cell, evoking an "eat-me" sign to the phagocytes. The detection of cell death in cells and tissues has gained immense therapeutic potential. Although many key proteins of the cell cycle machinery and apoptotic signaling pathway have been identified, the molecular mechanisms of these proteins are still not clear. This review attempts to summarize the fundamental aspects and the molecular mechanism of apoptosis, recent advances in detection methodologies, as well as some of the negative aspects of the applied techniques.